CONFORMATIONAL PREFERENCES OF A CHIMERIC PEPTIDE HIV-1 IMMUNOGEN FROMTHE C4-V3 DOMAINS OF GP120 ENVELOPE PROTEIN OF HIV-1 CANOA BASED ON SOLUTION NMR - COMPARISON TO A RELATED IMMUNOGENIC PEPTIDE FROM HIV-1 RF

A critical problem to overcome in HIV vaccine design is the variabilit y among HIV strains, One strategy to solve this problem is the constru ction of multicomponent immunogens reflective of common HIV motifs, Cu rrently, it is not known if these motifs should be based primarily on amino acid sequence or higher-order structure of the viral proteins or a combination of the two. In this paper, we report NMR-derived soluti on conformations for a synthetic peptide taken from the C4 and V3 doma ins of HIV-1 CAN0A gp120 envelope protein. This peptide, designated T1 -SP10CAN0(A), is compared to a recently reported C4-V3 peptide, T1-SP1 0RF(A) from the HIV-1 RF strain [de Lorimier et al. (1994) Biochemistr y 33, 2055-2062], in terms of conformational features and immune respo nses in mice [Haynes er al. (1995) AIDS Res. Hum. Retroviruses 11, 211 -221]. The T1 segment of 16 amino acids from the gp120 C4 domain is id entical in both peptides and exhibits nascent helical character. The S P10 region, taken from the gp120 V3 loop, differs from that of T1-SP10 RF(A) in both sequence and conformations, A reverse turn is observed a t the conserved GPGX sequence. The rest of the SP10 domain is extended with the exception of the last three residues which show evidence for a helical arrangement. Modeling of the turn region of the T1-SP10CAN0 (A) peptide shows exposure of a continuous apolar stretch of side chai ns similar to that reported in the crystal structure of a V3 peptide f rom HIV-1 MN complexed with a monoclonal antibody [Rini er al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6325-6329]. This hydrophobic patch i s interrupted by a charged Lys residue in the T1-SP10RF(A) peptide. Th is observation suggests that the HIV-1 CAN0A and HIV-1 RF C4-V3 peptid es can induce widely different anti-HIV antibodies, consistent with im munogenic results.