LIVIVO - Search results -

Search results

Result 1 - 10 of total 25

Search options

Article ; Online: New approaches to HIV protease inhibitor drug design II: testing the substrate envelope hypothesis to avoid drug resistance and discover robust inhibitors.

Nalam, Madhavi N L / Schiffer, Celia A

2009 Volume 3, Issue 6, Page(s) 642–646

Abstract: Purpose of review: Drug resistance results when the balance between the binding of inhibitors and the turnover of substrates is perturbed in favor of the substrates. Resistance is quite widespread to the HIV-1 protease inhibitors permitting the protease ...

Abstract	Purpose of review: Drug resistance results when the balance between the binding of inhibitors and the turnover of substrates is perturbed in favor of the substrates. Resistance is quite widespread to the HIV-1 protease inhibitors permitting the protease to process its 10 different substrates. This processing of the substrates permits the virus HIV-1 to mature and become infectious. The design of HIV-1 protease inhibitors that closely fit within the substrate-binding region is proposed to be a strategy to avoid drug resistance. Recent findings: Cocrystal structures of HIV-1 protease with its substrates define an overlapping substrate-binding region or substrate envelope. Novel HIV-1 protease inhibitors that were designed to fit within this substrate envelope were found to retain high binding affinity and have a flat binding profile against a panel of drug-resistant HIV-1 proteases. Summary: The avoidance of drug resistance needs to be considered in the initial design of inhibitors to quickly evolving targets such as HIV-1 protease. Using a detailed knowledge of substrate binding appears to be a promising strategy for achieving this goal to obtain robust HIV-1 protease inhibitors.
Language	English
Publishing date	2009-01-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0b013e3283136cee
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6812: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Synthese und Eigenschaften von 2-Cyanimino-l,3-dimethylimidazolin [1] / Synthesis and Properties of 2-Cyanimino-l,3-dimethylimidazoline [1]

Kuhn, Norbert / Martin Grathwohl / Manfred Steimann / Roland Boese / N. L. Madhavi Nalam

Zeitschrift für Naturforschung. 2014 June 2, v. 56, no. 10

2014

Abstract: 2-Cyanimino-1,3-dimethylimidazoline (3, ImNCN) is obtained from 1,3-dimethyl-2-iminoimidazoline (2) and BrCN. With Mo(CO)₆, 3 forms the carbonyl complex (ImNCN)Mo(CO)₅ (4). The crystal structure of 3 is reported. The properties of 3 are discussed on ... ...

Abstract	2-Cyanimino-1,3-dimethylimidazoline (3, ImNCN) is obtained from 1,3-dimethyl-2-iminoimidazoline (2) and BrCN. With Mo(CO)₆, 3 forms the carbonyl complex (ImNCN)Mo(CO)₅ (4). The crystal structure of 3 is reported. The properties of 3 are discussed on comparison with those of (R₂N)₂C=NCN (1, R = H).
Keywords	carbonyl compounds ; chemical reactions ; crystal structure ; molybdenum ; synthesis
Language	English
Dates of publication	2014-0602
Size	p. 1015-1019.
Publishing place	Verlag der Zeitschrift für Naturforschung
Document type	Article
ZDB-ID	124635-5
ISSN	0340-5087 ; 0044-3174 ; 0932-0776 ; 0341-0447 ; 0341-0420
ISSN	0340-5087 ; 0044-3174 ; 0932-0776 ; 0341-0447 ; 0341-0420
DOI	10.1515/znb-2001-1009
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 47/11 b: Show issues
Z 9.8: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Hydrophobic core flexibility modulates enzyme activity in HIV-1 protease.

Mittal, Seema / Cai, Yufeng / Nalam, Madhavi N L / Bolon, Daniel N A / Schiffer, Celia A

Journal of the American Chemical Society

2012 Volume 134, Issue 9, Page(s) 4163–4168

Abstract: Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic ... ...

Abstract	Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity.
MeSH term(s)	Crystallography, X-Ray ; Enzyme Activation ; HIV Protease/chemistry ; HIV Protease/genetics ; HIV Protease/metabolism ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Protein Conformation
Chemical Substances	HIV Protease (EC 3.4.23.-) ; p16 protease, Human immunodeficiency virus 1 (EC 3.4.23.-)
Language	English
Publishing date	2012-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja2095766
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Bonn / Germany

Z 4' 55/32: Show issues
Z 7.3: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Testing the substrate-envelope hypothesis with designed pairs of compounds.

Shen, Yang / Altman, Michael D / Ali, Akbar / Nalam, Madhavi N L / Cao, Hong / Rana, Tariq M / Schiffer, Celia A / Tidor, Bruce

ACS chemical biology

2013 Volume 8, Issue 11, Page(s) 2433–2441

Abstract: Acquired resistance to therapeutic agents is a significant barrier to the development of clinically effective treatments for diseases in which evolution occurs on clinical time scales, frequently arising from target mutations. We previously reported a ... ...

Abstract	Acquired resistance to therapeutic agents is a significant barrier to the development of clinically effective treatments for diseases in which evolution occurs on clinical time scales, frequently arising from target mutations. We previously reported a general strategy to design effective inhibitors for rapidly mutating enzyme targets, which we demonstrated for HIV-1 protease inhibition [Altman et al. J. Am. Chem. Soc. 2008, 130, 6099-6113]. Specifically, we developed a computational inverse design procedure with the added constraint that designed inhibitors bind entirely inside the substrate envelope, a consensus volume occupied by natural substrates. The rationale for the substrate-envelope constraint is that it prevents designed inhibitors from making interactions beyond those required by substrates and thus limits the availability of mutations tolerated by substrates but not by designed inhibitors. The strategy resulted in subnanomolar inhibitors that bind robustly across a clinically derived panel of drug-resistant variants. To further test the substrate-envelope hypothesis, here we have designed, synthesized, and assayed derivatives of our original compounds that are larger and extend outside the substrate envelope. Our designs resulted in pairs of compounds that are very similar to one another, but one respects and one violates the substrate envelope. The envelope-respecting inhibitor demonstrates robust binding across a panel of drug-resistant protease variants, whereas the envelope-violating one binds tightly to wild type but loses affinity to at least one variant. This study provides strong support for the substrate-envelope hypothesis as a design strategy for inhibitors that reduce susceptibility to resistance mutations.
MeSH term(s)	Computer Simulation ; Crystallography, X-Ray ; Drug Resistance, Viral/drug effects ; HIV Protease Inhibitors/chemistry ; HIV Protease Inhibitors/pharmacology ; HIV-1/drug effects ; Humans ; Inhibitory Concentration 50 ; Models, Molecular ; Mutation ; Substrate Specificity ; Viral Structural Proteins/chemistry ; Viral Structural Proteins/metabolism
Chemical Substances	HIV Protease Inhibitors ; Viral Structural Proteins
Language	English
Publishing date	2013-09-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/cb400468c
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Design, synthesis, and biological and structural evaluations of novel HIV-1 protease inhibitors to combat drug resistance.

Parai, Maloy Kumar / Huggins, David J / Cao, Hong / Nalam, Madhavi N L / Ali, Akbar / Schiffer, Celia A / Tidor, Bruce / Rana, Tariq M

Journal of medicinal chemistry

2012 Volume 55, Issue 14, Page(s) 6328–6341

Abstract: A series of new HIV-1 protease inhibitors (PIs) were designed using a general strategy that combines computational structure-based design with substrate-envelope constraints. The PIs incorporate various alcohol-derived P2 carbamates with acyclic and ... ...

Abstract	A series of new HIV-1 protease inhibitors (PIs) were designed using a general strategy that combines computational structure-based design with substrate-envelope constraints. The PIs incorporate various alcohol-derived P2 carbamates with acyclic and cyclic heteroatomic functionalities into the (R)-hydroxyethylamine isostere. Most of the new PIs show potent binding affinities against wild-type HIV-1 protease and three multidrug resistant (MDR) variants. In particular, inhibitors containing the 2,2-dichloroacetamide, pyrrolidinone, imidazolidinone, and oxazolidinone moieties at P2 are the most potent with K(i) values in the picomolar range. Several new PIs exhibit nanomolar antiviral potencies against patient-derived wild-type viruses from HIV-1 clades A, B, and C and two MDR variants. Crystal structure analyses of four potent inhibitors revealed that carbonyl groups of the new P2 moieties promote extensive hydrogen bond interactions with the invariant Asp29 residue of the protease. These structure-activity relationship findings can be utilized to design new PIs with enhanced enzyme inhibitory and antiviral potencies.
MeSH term(s)	Chemistry Techniques, Synthetic ; Crystallography, X-Ray ; Drug Design ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Viral/drug effects ; HIV Protease/chemistry ; HIV Protease/metabolism ; HIV Protease Inhibitors/chemical synthesis ; HIV Protease Inhibitors/chemistry ; HIV Protease Inhibitors/pharmacology ; HIV-1/drug effects ; HIV-1/enzymology ; Models, Molecular ; Protein Conformation ; Structure-Activity Relationship
Chemical Substances	HIV Protease Inhibitors ; HIV Protease (EC 3.4.23.-) ; p16 protease, Human immunodeficiency virus 1 (EC 3.4.23.-)
Language	English
Publishing date	2012-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm300238h
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Drug resistance conferred by mutations outside the active site through alterations in the dynamic and structural ensemble of HIV-1 protease.

Ragland, Debra A / Nalivaika, Ellen A / Nalam, Madhavi N L / Prachanronarong, Kristina L / Cao, Hong / Bandaranayake, Rajintha M / Cai, Yufeng / Kurt-Yilmaz, Nese / Schiffer, Celia A

Journal of the American Chemical Society

2014 Volume 136, Issue 34, Page(s) 11956–11963

Abstract: HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination ...

Abstract	HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRV-protease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure and dynamic ensemble of HIV-1 protease active site. These alterations correlate with the observed inhibitor binding affinities for the mutants, and suggest a network hypothesis on how the effect of distal mutations are propagated to pivotal residues at the active site and may contribute to conferring drug resistance.
MeSH term(s)	Binding Sites ; Darunavir ; Drug Resistance, Viral/genetics ; HIV Protease/chemistry ; HIV Protease/genetics ; HIV Protease/metabolism ; HIV Protease Inhibitors/pharmacology ; HIV-1/enzymology ; Models, Molecular ; Mutation ; Protein Binding ; Protein Conformation ; Sulfonamides/pharmacology
Chemical Substances	HIV Protease Inhibitors ; Sulfonamides ; HIV Protease (EC 3.4.23.-) ; Darunavir (YO603Y8113)
Language	English
Publishing date	2014-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja504096m
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Bonn / Germany

Z 4' 55/32: Show issues
Z 7.3: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Hydrophobic Core Flexibility Modulates Enzyme Activity in HIV-1 Protease

Mittal, Seema / Bolon Daniel N. A / Cai Yufeng / Nalam Madhavi N. L / Schiffer Celia A

Journal of the American Chemical Society. 2012 Mar. 07, v. 134, no. 9

2012

Abstract	Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity.
Keywords	active sites ; alkylation ; crosslinking ; crystal structure ; disulfide bonds ; drug resistance ; enzyme activity ; Human immunodeficiency virus 1 ; hydrophobicity ; mass spectrometry ; molecular dynamics ; mutation ; pathogenicity ; proteinases
Language	English
Dates of publication	2012-0307
Size	p. 4163-4168.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021%2Fja2095766
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 55/32: Show issues
Z 7.3: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Molecular Basis for Drug Resistance in HIV-1 Protease.

Ali, Akbar / Bandaranayake, Rajintha M / Cai, Yufeng / King, Nancy M / Kolli, Madhavi / Mittal, Seema / Murzycki, Jennifer F / Nalam, Madhavi N L / Nalivaika, Ellen A / Özen, Ayşegül / Prabu-Jeyabalan, Moses M / Thayer, Kelly / Schiffer, Celia A

Viruses

2010 Volume 2, Issue 11, Page(s) 2509–2535

Abstract: HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the ... ...

Abstract	HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease's function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.
Language	English
Publishing date	2010-11-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v2112509
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease.

Nalam, Madhavi N L / Peeters, Anik / Jonckers, Tim H M / Dierynck, Inge / Schiffer, Celia A

Journal of virology

2007 Volume 81, Issue 17, Page(s) 9512–9518

Abstract: Human immunodeficiency virus type 1 (HIV-1) protease has been continuously evolving and developing resistance to all of the protease inhibitors. This requires the development of new inhibitors that bind to the protease in a novel fashion. Most of the ... ...

Abstract	Human immunodeficiency virus type 1 (HIV-1) protease has been continuously evolving and developing resistance to all of the protease inhibitors. This requires the development of new inhibitors that bind to the protease in a novel fashion. Most of the inhibitors that are on the market are peptidomimetics, where a conserved water molecule mediates hydrogen bonding interactions between the inhibitors and the flaps of the protease. Recently a new class of inhibitors, lysine sulfonamides, was developed to combat the resistant variants of HIV protease. Here we report the crystal structure of a lysine sulfonamide. This inhibitor binds to the active site of HIV-1 protease in a novel manner, displacing the conserved water and making extensive hydrogen bonds with every region of the active site.
MeSH term(s)	Binding Sites ; Crystallography, X-Ray ; HIV Protease/chemistry ; HIV Protease/metabolism ; HIV Protease Inhibitors/chemistry ; HIV Protease Inhibitors/metabolism ; Models, Molecular ; Protein Structure, Tertiary ; Sulfonamides/chemistry ; Sulfonamides/metabolism
Chemical Substances	HIV Protease Inhibitors ; Sulfonamides ; HIV Protease (EC 3.4.23.-)
Language	English
Publishing date	2007-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00799-07
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Drug Resistance Conferred by Mutations Outside the Active Site through Alterations in the Dynamic and Structural Ensemble of HIV-1 Protease

Ragland, Debra A / Bandaranayake Rajintha M / Cai Yufeng / Cao Hong / Kurt-Yilmaz Nese / Nalam Madhavi N. L / Nalivaika Ellen A / Prachanronarong Kristina L / Schiffer Celia A

Journal of the American Chemical Society. 2014 Aug. 27, v. 136, no. 34

2014

Abstract	HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRVâprotease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure and dynamic ensemble of HIV-1 protease active site. These alterations correlate with the observed inhibitor binding affinities for the mutants, and suggest a network hypothesis on how the effect of distal mutations are propagated to pivotal residues at the active site and may contribute to conferring drug resistance.
Keywords	active sites ; antiretroviral agents ; binding capacity ; crystal structure ; drug resistance ; HIV infections ; Human immunodeficiency virus 1 ; molecular dynamics ; mutants ; mutation ; proteinase inhibitors ; proteinases ; therapeutics
Language	English
Dates of publication	2014-0827
Size	p. 11956-11963.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021%2Fja504096m
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 55/32: Show issues
Z 7.3: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED