title: Total synthesis, characterization, and conformational analysis of the naturally occurring hexadecapeptide integramide A and a diastereomer.
abstract: Integramide A is a 16-amino acid peptide inhibitor of the enzyme HIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L-Iva(14)-D-Iva(15). Herein, we describe the syntheses of the natural compound and its D-Iva(14)-L-Iva(15) 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.
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry University of Padova via Marzolo 1, 35131 Padova, Italy.
authors: Marta
authors: M
authors: De Zotti
authors: Francesca
authors: F
authors: Damato
authors: Fernando
authors: F
authors: Formaggio
authors: Marco
authors: M
authors: Crisma
authors: Elisabetta
authors: E
authors: Schievano
authors: Stefano
authors: S
authors: Mammi
authors: Bernard
authors: B
authors: Kaptein
authors: Quirinus B
authors: QB
authors: Broxterman
authors: Peter J
authors: PJ
authors: Felock
authors: Daria J
authors: DJ
authors: Hazuda
authors: Sheo B
authors: SB
authors: Singh
authors: Jochen
authors: J
authors: Kirschbaum
authors: Hans
authors: H
authors: Brückner
authors: Claudio
authors: C
authors: Toniolo
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004151:Dipeptides / Q000737:chemistry*; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D004151:Dipeptides; D019428:HIV Integrase Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; C456979:integramide A; D019427:HIV Integrase