Dimitrios Krikorian

The Presence of Antibodies Recognizing a Peptide Derived from the Second Conserved Region of HIV-1 gp120 Correlates with Non-Progressive HIV Infection

The C-terminus of the second conserved region of HIV-1 gp120 represents a functionally important domain, as it encompasses amino acids directly involved in the binding to the CD4 receptor and in post-receptor binding events. Previous studies have suggested that antibodies with specific affinity to a 23 amino acids-long NTM polypeptide, derived from this HIV-1 gp120 domain, may be involved in the control of HIV disease progression. In the current work, we searched for NTM-recognizing antibodies in specific cohorts of HIV-1 infected individuals, including long-term nonprogressors (LTNP) and progressors. For this purpose, we employed a previously defined bioinformatics criterion for design of an NTM peptide mimetic to select an octapeptide, NTMs (FTDNAKTI), which is more suitable for use in a solid-state enzyme-linked immunosorbent assay (ELISA). Our results show that NTMs-reactive antibodies are significantly more prevalent (p < 0.01) in LTNP as compared to progressors and healthy control subjects, indicating their association with non-progressive infection. The presence of antibodies recognizing the second conserved region of the HIV-1 gp120 derived peptide, NTMs, in LTNP sera suggest that these antibodies could be of considerable interest for development of anti-HIV immune-based therapies and vaccines.

A complementary La/SSB epitope anchored to Sequential Oligopeptide Carrier regulates the anti-La/SSB response in immunized animals.

Complementary peptide epitopes, derived from complementary RNA sequences, have been used for suppressing the autoimmune response in experimental autoimmune diseases as myasthenia gravis, allergic neuritis and allergic encephalomyelitis. Aiming at contributing to the development of a tool that could regulate the autoantibody production against La/SSB, which is the main target of autoantibodies in Sjogrens syndrome (SS) and systemic lupus erythematosus (SLE), the complementary epitope, cpep349–364, of the minor T/major B cell epitope of La/SSB, pep349–364, was utilized for the induction of neutralizing anti‐cpep349–364 antibodies in rabbit immunizations. Complementary peptides were coupled to an artificial carrier, developed in our laboratory, in order to enhance the complementary potency of cpep349–364 and its counterpart. This carrier, named Sequential Oligopeptide Carrier, SOCn, formed by the repeating tripeptide Lys‐Aib‐Gly, adopts helical conformation, which allows the anchored peptide epitopes to preserve their initial reactivity such as molecular recognition, antigenicity/immunogenicity. Our study provides proof of evidence of specific interactions between idiotypic (Id)/anti‐idiotypic (anti‐Id) antibodies generated in immunized animals by the sense epitope (conjugate I) of La/SSB and its complementary counterpart (conjugate II). It was also demonstrated that the Id/anti‐Id association is specifically disrupted by adding either the sense epitope (conjugate I) or its complementary counterpart (conjugate II). A mutual neutralization of Id/anti‐Id antibodies was observed in vivo, which implies that generation of anti‐Id antibodies by immunization with the complementary La/SSB epitope could scavenge the anti‐La/SSB response. Copyright

Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin

Anoplin is a short natural cationic antimicrobial peptide which is derived from the venom sac of the solitary wasp, Anoplius samariensis. Due to its short sequence G1LLKR5IKT8LL‐NH2, it is ideal for research tests. In this study, novel analogs of anoplin were prepared and examined for their antimicrobial, hemolytic activity, and proteolytic stability. Specific substitutions were introduced in amino acids Gly1, Arg5, and Thr8 and lipophilic groups with different lengths in the N‐terminus in order to investigate how these modifications affect their antimicrobial activity. These cationic analogs exhibited higher antimicrobial activity than the native peptide; they are also nontoxic at their minimum inhibitory concentration (MIC) values and resistant to enzymatic degradation. The substituted peptide GLLKF5IKK8LL‐NH2 exhibited high activity against Gram‐negative bacterium Zymomonas mobilis (MIC = 7 µg/ml), and the insertion of octanoic, decanoic, and dodecanoic acid residues in its N‐terminus increased the antimicrobial activity against Gram‐positive and Gram‐negative bacteria (MIC = 5 µg/ml). The conformational characteristics of the peptide analogs were studied by circular dichroism. Structure activity studies revealed that the substitution of specific amino acids and the incorporation of lipophilic groups enhanced the amphipathic α‐helical conformation inducing better antimicrobial effects. Copyright