Peptides from the inside of the antibodies are active against infectious agents and tumours

Abstract

Synthetic peptides, representative of sequences related to the complementarity determining regions and constant region of antibodies, proved to exert in vitro, ex vivo and/or in vivo antimicrobial, antiviral, anti-tumour and/or immunomodulatory activities, conceivably mediated by different mechanisms of action and regardless of the specificity and isotype of the belonging immunoglobulin. Antibody-derived peptides can show intrinsic properties of self-aggregation in β structures, able to assemble on molecular targets and dissociate spontaneously, leading to the formation of hydrogels. Whilst the self-assembled state may provide protection against proteases and the slow kinetic of dissociation assures a release of the active form over time, the receptor affinity is responsible for targeted delivery. Peptides derived from single amino acid substitution of bioactive antibody fragments, adopted as surrogates of natural point mutations, displayed further differential biological activities. Overall, these observations allow to envisage that antibodies could represent an unlimited source of new anti-infective and anti-tumour peptides.

Generation of monoclonal antibodies against mitocryptide‐2: toward a new strategy to investigate the biological roles of cryptides

“…After our findings, many bioactive fragmented peptides derived from various functional proteins including hemoglobin and proteinase-activated receptor 1 have been identified [6][7][8][9][10][11][12], and thus, it is of keen interest to investigate their physiological significance. However, it is difficult to elucidate the physiological roles of those cryptides.…”

“…The hMCT-2 (9-15) and hMCT-2 (10-15) peptides inhibited NhM2A1 binding to the plate with similar potencies. On the other hand, the inhibitory effects of hMCT-2 (11)(12)(13)(14)(15) and hMCT-2 (12)(13)(14)(15) were dramatically decreased in comparison with that of hMCT-2 (10)(11)(12)(13)(14)(15). These results demonstrate that an NhM2A1-binding epitope is located within hMCT-2 (10-15).…”

“…These results indicate that the epitope is located in the C-terminal region of hMCT-2. hMCT-2 (10-15), hMCT-2 (11)(12)(13)(14)(15), and 2 (12)(13)(14)(15), which are truncated derivatives of hMCT-2 (9-15), were then examined for the elucidation of its epitope. The hMCT-2 (9-15) and hMCT-2 (10-15) peptides inhibited NhM2A1 binding to the plate with similar potencies.…”

“…Because NhM2A1 was bound to hMCT-2 (10)(11)(12)(13)(14)(15), it was also investigated whether NhM2A1 recognized a cleavage site in hMCT-2 that is generated upon its hydrolysis from cytochrome b (Figure 2(B)). NhM2A1 binding (10 nM) to the plate was almost completely prevented by 3 μM hMCT-2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…Because NhM2A1 was bound to hMCT-2 (10)(11)(12)(13)(14)(15), it was also investigated whether NhM2A1 recognized a cleavage site in hMCT-2 that is generated upon its hydrolysis from cytochrome b (Figure 2(B)). NhM2A1 binding (10 nM) to the plate was almost completely prevented by 3 μM hMCT-2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). In contrast, 3 μM hMCT-2 (1-16), hMCT-2 (1-17), and hMCT-2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), which are hMCT-2 derivatives that are C-terminally elongated with the same amino acid residues that cytochrome b has, did not inhibit the binding of NhM2A1 to the plate (Figure 2(B)).…”