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1.
Org Biomol Chem ; 9(16): 5762-5, 2011 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-21720634

RESUMO

This article describes a model peptide that concurrently displays both α- and ß-turns, as demonstrated by structural investigations using single crystal X-ray crystallography and solution-state NMR studies. The motif reported herein has the potential for the design of novel conformationally ordered synthetic oligomers with structural architectures distinct from those classically observed.


Assuntos
Peptídeos/química , Motivos de Aminoácidos , Cristalografia por Raios X , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína
2.
J Med Chem ; 45(18): 3953-62, 2002 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-12190317

RESUMO

In an effort to discover potent antibacterials based on the entropically favored "bioactive conformation" approach, we have designed and synthesized a series of novel tricyclic molecules mimicking the conformationally constrained structure of the oxazolidinone antibacterial, Linezolid 1. The structure 3 obtained by this approach was synthesized and found to be moderately active against a panel of Gram-positive organisms tested. Further introduction of a fluorine atom in the aromatic ring of compound 3 as in Linezolid resulted in some excellent compounds possessing potent antibacterial activity. The thus obtained lead molecule 16 was further fine-tuned by structure-activity relationship studies on the amide functionality leading to a number of novel tricyclic oxazolidinone derivatives. Some particularly interesting compounds include the thioamides 36 and 37, thiocarbamate 41, and thiourea 45. The in vitro activity results of amide homologues of 16 (compounds 25-30) revealed that compounds up to four carbon atoms on the amide nitrogen retain the activity. In general, thioamides and thiocarbamates are more potent when compared to the corresponding amides and carbamates.


Assuntos
Acetamidas/síntese química , Antibacterianos/síntese química , Oxazolidinonas/síntese química , Acetamidas/química , Acetamidas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linezolida , Testes de Sensibilidade Microbiana , Conformação Molecular , Mimetismo Molecular , Oxazolidinonas/química , Oxazolidinonas/farmacologia , Relação Estrutura-Atividade , Resistência a Vancomicina
3.
J Org Chem ; 72(18): 7022-5, 2007 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-17691737

RESUMO

In this note, we describe the design, synthesis, and structural studies of novel hybrid foldamers derived from Aib-Pro-Adb building blocks that display repeat beta-turn structure motif. The foldamer having a conformationally constrained aliphatic-aromatic amino acid conjugate adopts a well-defined, compact, three-dimensional structure, governed by a combined conformational restriction imposed by the individual amino acids with which it is made of. Conformational investigations by single-crystal X-ray and solution-state NMR studies were undertaken to investigate the conformational preference of these foldamers with a hetero-backbone. Our findings suggest that constrained aliphatic-aromatic amino acid conjugates would offer new avenues for the de novo design of hybrid foldamers with distinctive structural architectures.


Assuntos
Aminoácidos Aromáticos/química , Ácidos Graxos/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Terciária de Proteína , Titulometria
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