1/2/2023 0 Comments Phenolic trminal pinsKeywords: Protegrin, gelatinases, MMP-2, MMP-9, oncostatin M, TGBβ, interleukin-6 However, other C-terminal peptides of the more than 500 members of the serpin superfamily could be potential anti-infective agents. C-terminal peptides derived from serpins B9 (anti-granzyme B) and C1 (antithrombin III) were not as active as A1-C26. VIRIP does not have the complete internalization sequence and does not affect HIV-1 promoter activity but effectively blocks HIV-1 entry by binding to the fusion peptide of gp41, a crucial component of the HIV envelope glycoprotein complex. VIRIP (serpin A1(353-372), virus-inhibitory peptide) is a serpin A1 fragment isolated from hemofiltrates of patients with chronic kidney failure. Synthetic peptides based on this sequence go to the nucleus few minutes after cell membrane interaction. A1- C26 contains a putative internalization signal pentapeptide FVFLM. CD91 also internalizes the antiviral defensins, structurally similar to A1-C26. The major receptor involved in internalization of A1-C36 and many serpin-proteinase complexes is CD91, a protein highly expressed in HIV-1-infected true non-progressors. A1- C36, the C-terminal peptide produced after serpin-proteinase complex formation is probably responsible for this intracellular anti-HIV activity because the synthetic, truncated 26-residue peptide A1-C26, comprising the complete β-hairpin structure of A1-C36, strongly inhibited HIV-1 expression in infected cells. Surprisingly, serpin A1 inhibited as well HIV-1 replication and promoter activity. Antiviral activity could be explained by the capacity of serpin A1 to prevent binding of the HIV envelope glycoprotein to proteinases associated with host cell membranes. The observation that proteinases located at the surface of HIV-1 target cells were involved in viral infection led to the discovery of the anti-HIV-1 properties of serpin A1(α1-proteinase inhibitor, α1-antitrypsin).
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