Linked Life Data

11473415

Source:http://linkedlifedata.com/resource/pubmed/id/11473415

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-7-27
pubmed:abstractText
From the screening of a microbial extract library, isocomplestatin (1), a new axial-chiral isomer of complestatin (2) which is a known rigid bicyclic hexapeptide, was identified as a potent natural product inhibitor of HIV-1 integrase, a unique enzyme responsible for viral replication. Isocomplestatin showed inhibitory activities (IC(50)) in coupled 3'-end processing/strand transfer (200 nM), strand transfer (4 microM), and HIV-1 replication (200 nM) in virus-infected cells. Attempted large-scale isolation of 1 by the literature method, used for the isolation of complestatin, led to lower yield and limited availability. We have developed several new, two-step, high-yielding absorption/elution methods of isolation based on reverse-phase chromatography at pH 8 that are applicable to scales from one gram to potential industrial quantities. We have also discovered and determined the structure of two new congeners of 1, namely, complestatins A (4) and B (5), with almost equal HIV-1 integrase activity. They differ from 1 at C2' and C3' of the tryptophan moiety (residue F). Selective acid hydrolysis of chloropeptin I (3), itself a known acid-catalyzed rearranged isomer of 1 and 2 (8'- vs 7'-substitution in tryptophan residue F, respectively), an isomer of complestatin, and isocomplestatin resulted in a number of fragments (6-10) with retention of most of the HIV-1 integrase activity. The structure-activity relationship as revealed by these compounds could possibly lead to the design of better inhibitors or understanding of the HIV-1 integrase target.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0163-3864
pubmed:author
pubmed:issnType
Print
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
874-82
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11473415-Anti-HIV Agents, pubmed-meshheading:11473415-Antigens, CD45, pubmed-meshheading:11473415-Chlorophenols, pubmed-meshheading:11473415-Chromatography, High Pressure Liquid, pubmed-meshheading:11473415-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:11473415-HIV Envelope Protein gp120, pubmed-meshheading:11473415-HIV Integrase, pubmed-meshheading:11473415-HIV Integrase Inhibitors, pubmed-meshheading:11473415-HIV-1, pubmed-meshheading:11473415-Magnetic Resonance Spectroscopy, pubmed-meshheading:11473415-Models, Chemical, pubmed-meshheading:11473415-Molecular Structure, pubmed-meshheading:11473415-Oligopeptides, pubmed-meshheading:11473415-Peptides, Cyclic, pubmed-meshheading:11473415-Stereoisomerism, pubmed-meshheading:11473415-Streptomyces, pubmed-meshheading:11473415-Structure-Activity Relationship
pubmed:year
2001
pubmed:articleTitle
The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I.
pubmed:affiliation
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
pubmed:publicationType
Journal Article