Anti-HIV activity and conformational studies of peptides derived from the C-terminal sequence of SDF-1.
The entry of the human immunodeficiency virus type 1 (HIV-1) into target cells requires the interaction of viral envelope glycoprotein, gp120, with the human CD4 glycoprotein and a chemokine receptor, usually CCR5 or CXCR4. The natural ligand for CXCR4 is the chemokine SDF-1 that inhibits entry and replication of X4 HIV-1 strains. SDF-1 is produced in two forms, SDF-1alpha (68 residues) and SDF-1beta (72 residues); the difference between them lies in the additional four C-terminal amino acids in the SDF-1beta sequence. Despite the relevance of the N-terminal site in determining the SDF anti HIV-1 activity, SDF-1beta has a stronger activity than SDF-1alpha. Here we demonstrate that a synthetic peptide mapped on the C-terminus of SDF-1beta presents inhibitory activity, whereas an analogue reproducing the C-terminal trait of SDF-1alpha does not show any activity. The opposite biological effect of the two peptides correlates with the type of interaction they each have with heparin and chondroitin sulfate.
Dettin
Monica
M
Department of Chemical Process Engineering, University of Padua, 35131 Padua, Italy. monica.dettin@unipd.it
Pasquato
Antonella
A
Scarinci
Claudia
C
Zanchetta
Marisa
M
De Rossi
Anita
A
Di Bello
Carlo
C
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000737:chemistry; D002942:Circular Dichroism; D016207:Cytokines / Q000737:chemistry*; D006678:HIV / Q000187:drug effects; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D010446:Peptide Fragments; D010455:Peptides; D006493:Heparin; D002809:Chondroitin Sulfates