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. 1992 Jul 1;89(13):5872–5876. doi: 10.1073/pnas.89.13.5872

Design and synthesis of a CD4 beta-turn mimetic that inhibits human immunodeficiency virus envelope glycoprotein gp120 binding and infection of human lymphocytes.

S Chen 1, R A Chrusciel 1, H Nakanishi 1, A Raktabutr 1, M E Johnson 1, A Sato 1, D Weiner 1, J Hoxie 1, H U Saragovi 1, M I Greene 1, et al.
PMCID: PMC49399  PMID: 1352879

Abstract

Poor bioavailability, rapid degradation, antigenicity, and high cost often limit the use of proteinaceous pharmaceuticals. One goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of complex proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. We have developed a reverse-turn mimetic system to explore peptide and protein structure-function relationships. We now report the design and synthesis of a small molecule (M(r) 810, as its trifluoroacetate salt), water soluble, proteolytically stable mimetic of residues Gln40-Thr45 of the complementarity-determining 2-like region of CD4. This mimetic has a low micromolar Kd for human T-lymphotropic virus type IIIB gp120 and reduces syncytium formation.

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Selected References

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