A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.

Abstract

A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constrcted with specificity to a neutalization-indudng region of human immunodeficiency virus type 1 (1HV-1). The mAb has its major reactivity to the amino acid sequence I-GPGRA in the V3 viral envelope region. All CDRs including several framework amno acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy-and light-chain variable d . Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the olher CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemicaly modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cels. Both the homologous lllB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of IRV-infected persons.

The Cyclization and Polymerization of Bacterially Expressed Proteins Using Modified Self-splicing Inteins

“…This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Synthetic genes based on brain-binding peptide (BBP) (20), the cyclic RGD containing decapeptide (RGD) (21), and CDR-H3/C2 (22) were inserted into the SapI sites of pBSCXB1 to create pBBP1, pRGD1, and pCDR1, respectively. The synthetic oligonucleotides were BBP.fw, 5Ј-AAT TGC CTG TCT TCC CGT CTG GAT GCT ATG-3Ј, and BBP.rv, 5Ј-GCA CAT AGC ATC CAG ACG GGA AGA CAG GCA-3Ј; for the RGD gene they were cRGD1.fw, 5Ј-AAT TGT CGT GGT GAT TTC CCG GCT CTC GAG ATG-3Ј, and cRGD1.rv, 5Ј-GCA CAT CTC GAG AGC CGG GAA ATC ACC ACG ACA-3Ј; and for the CDR-H3/C2 gene they were CDR.fw, 5Ј-AAT TGC GCT CTG ATC TAT TAC GAT TAT GAA GAG GAC TAT TAC TTC GAT ATG-3Ј, and CDR.rv, 5Ј-GCA CAT ATC GAA GTA ATA GTC CTC TTC ATA ATC GTA ATA GAT CAG AGC GCA-3Ј.…”

“…BBP has been reported to target phage to specific organs in mice (20), RGD inhibits platelet aggregation (21), and CDR-H3/C2 has been shown to inhibit HIV-1 replication (22). Previously, these peptides were cyclized by chemical synthesis with an N-and C-terminal cysteine followed by oxidization to form a disulfide bond.…”

“…Upon incubation this protein formed cyclic and/or polymeric species. This approach, termed the TWIN (two intein) system, allowed the facile isolation of circular peptides involved in organ-specific localization (20), inhibition of platelet aggregation (21), and inhibition of HIV-1 replication (22). Furthermore, future studies on protein polymerization may allow the production and investigation of analogs of fibrous proteins, such as silk.…”

Antifungal and antitumor models of bioactive protective peptides

“…Although all CDRs are expected to contribute to antigen binding with variable affinity, only the CDR 3 from V H when tested as an isolated linear or cyclic peptide was found to have the same specificity of the original antibody, sharing some of its biological properties. V H CDR3 (H3) peptides with such properties have thus been called micro (mini) antibodies (Levi et al 1993, Bourgeois et al 1998. They can even compete with the antibody for binding to a certain antigen.…”

Computational Identification of Antigen-Binding Antibody Fragments

“…Several studies have shown that linear peptides containing one or more of the CDRs retain Ag specificity and bind it even as peptides (17)(18)(19)(20)(21)(22)(23)(24). Typically, the affinity of such peptides was in the high micromolar range, but, given their specificity, it has been shown that with relatively minor modifications they could become strong binders (22,25).…”