Molecular structures of CPF-dipeptides, inhibitors for the binding of CD4 with gp120.
The dipeptides N-carbomethoxycarbonyl-prolyl-phenylalanyl-benzyl esters (CPFs) play a significant role in the prevention of HIV-1 virus infection by interacting with the glycoprotein gp120, one of the envelope proteins of the HIV-1 virus. Of the four possible isomers of CPF, (L-pro-L-phe), (L-pro-D-phe), (D-pro-L-phe) and (D-pro-D-phe), herein denoted LL etc., the crystal structures of LL, stereoisomeric LD and the racemic mixture of LD/DL have been determined. All three peptides crystallize in the orthorhombic system and they all have similar cell dimensions: (i) LL, P2(1)2(1)2(1), a = 13.699(2), b = 25.893(5), c = 6.155(1) A, Z = 4, Dcale = 1.333 g cm-3, R = 0.070 for 1247 observed reflections; (ii) LD, P2(1)2(1)2(1), a = 11.663(2), b = 26.557(2), c = 7.281(1) A, Z = 4, Dcalc = 1.290 g cm-3, R = 0.054 for 1918 observed reflections; (iii) LD/DL, Pbc2(1), a = 11.953(2), b = 24.208(8), c = 7.782(2) A, Z = 4, Dcalc = 1.292 g cm-3, R = 0.080 for 894 observed reflections. Both the enantiomeric LD and the LD in racemic LD/DL have a similar conformation, an extended peptide chain with phi 1 = -76, -73 degrees; psi 1 = 160, 158 degrees, psi 2 = 123, 131 degrees and psi 2 = -172, -167 degrees, while peptide LL adopts a bent conformation at the Phe residue, phi 1 = -69 degrees, psi 1 = 158 degrees, phi 2 = -60 degrees and psi 2 = -34 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)
Venkatramani
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Department of Chemistry & Biochemistry, University of Oklahoma, Norman.
Hossain
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MB
Van der Helm
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D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D016281:Oncogene Protein gp140(v-fms) / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001593:Benzyl Compounds; D015704:CD4 Antigens; D004151:Dipeptides; D015699:HIV Envelope Protein gp120; D016281:Oncogene Protein gp140(v-fms); C067667:N-carbomethoxycarbonyl-prolyl-phenylalanyl-benzyl ester