Integramide A is a 16-amino acid peptide inhibitor of the enzymeHIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L-Iva14-D-Iva15. Herein, we describe the syntheses of the natural compound and its D-Iva14-L-Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques).These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy.
Synthesis and Conformational Analysis of Natural Peptide Inhibitor of HIV-1 Integrase.
DE ZOTTI, MARTA;FORMAGGIO, FERNANDO;SCHIEVANO, ELISABETTA;MAMMI, STEFANO;TONIOLO, CLAUDIO
2009
Abstract
Integramide A is a 16-amino acid peptide inhibitor of the enzymeHIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L-Iva14-D-Iva15. Herein, we describe the syntheses of the natural compound and its D-Iva14-L-Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques).These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy.
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