Peptidomimetics molecular modeling

Peptide chimeras of this type have proven extremely valuable for the examination of an array of recognition events. In conjunction with molecular modeling, peptidomimetic substrates and inhibitors of human thrombin were designed and synthesized to evaluate our proposed structure for the thrombin-bound conformation of fibrinopeptide A (Scheme 2i)J%]... 

Molecular modeling calculations using ab initio methods (MP2/6-31+G ) predict that spiro-(3-lactam of type M adopt a (3-tum secondary structure [50] which is very close to the ideal type-III (3-tums. Thus, these spiro-(3-lactams are the important members of the core for the preparation of different types of peptidomimetics using well-established chemistry. They combine the structural features required for inducing (3-tum motif. 

This perspective has examined the approaches to molecular modeling and drug design and emphasized their limitations. The reader should be aware, however, that these tools are daily used on many problems of therapeutic interest with increasing success. This is clearly witnessed by publications of such studies in almost every issue of current major journals. For specific application areas, such as RNA (490, 491), DNA (492-496), membrane (497-507), or peptidomimetic modeling (382, 508-513), the reader is referred to the literature. The prediction of molecular properties, such as log P and correlation between substructures and metabolism, has led to a dramatic increase in efforts to correlate adsorption, distribution (514), metabolism (515-617), and elimination (ADME) with chemical... 

Wolfe MS, Xia WM, Moore CL, Leather-wood DD, Ostaszewski BL, et al. 1999. Peptidomimetic probes and molecular modeling suggest Alzheimer s y-secre-tase is an intramembrane-cleaving as-partyl protease. Biochemistry 38 4720-27... 

Molecular modeling Peptidomimetics Metabolomics Pharmacogenomics Toxicogenomics Bioinformatics RNA silencing... 

The authors used the information gleaned from these studies to design the closely related chloromethyl ketone inhibitor of thrombin FPAM (68). Molecular modeling of this proposed inhibitor docked in the thrombin active site indicated that interactions similar to those important to fibrinopeptide binding could be obtained. Subsequent X-ray crystal structure analysis of the 68-thrombin complex was supportive of the peptidomimetic hypothesis,... 

T. Yamazaki, Y.-F. Zhu, A. ProbstI, R. K. Chadha, and M. Goodman, J. Org. Chem., 56, 6644 (1991). Probing a Molecular Model of Taste Utilizing Peptidomimetic Stereoisomers of 2-Aminocyclopentanecarboxylic Acid Methyl Ester. 

B, Donkor lO, Selkoe DJ. Peptidomimetic probes and molecular 36. modeling suggest Alzheimer s y-secretases are intramembranecleaving aspartyl proteases. Biochemistry 1999 38 4720-4727. 

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