HLA-DQ7 beta(1) and beta(2) derived peptides as immunomodulators.

Modulation of protein-protein interactions involved in the immune system by using small molecular mimics of the contact interfaces may lead to the blockage of the autoimmune response and the development of drugs for immunotherapy. The nonpolymorphic beta-regions, exposed to the microenvironment, of the modeled HLA-DQ7, which is genetically linked to autoimmune diseases, were determined. Peptides 132-141 and 58-67, located at the beta(1) and beta(2) domains of HLA-DQ7, respectively, were tested for their involvement in the interactions with CD4(+) T lymphocytes.

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 Sjogren's 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.

A palmitoyl-tailed sequential oligopeptide carrier for engineering immunogenic conjugates.

The main guideline in designing effective immunogens as vaccine candidates capable of eliciting potent and specific immune responses is to combine B/T cell epitopes and adjuvants as immunostimulators on the same carrier that links the major histocompatibility complex with T cell receptors. Aiming at contributing to the development of carriers for human usage a helicoid type sequential oligopeptide carrier, SOC(n)-II, formed by the repeating tetrapeptide unit (Aib-Lys-Aib-Gly)(n), n=2-7, elongated from the amino-terminus by the palmitoyl group, known for its adjuvanticity, is now presented. The main B cell epitope, PPGMRPP, of the Sm autoantigen against which the majority of antibodies in patients with systemic lupus erythematosus is directed, was coupled to the Lys-N(epsilon)H(2) groups of the carrier in four copies and the resulting conjugate Palm-SOC(4)-II-Sm(4) was subjected to animal immunizations without utilizing any adjuvant.

Design and synthesis of cationic Aib-containing antimicrobial peptides: conformational and biological studies.

Development of antimicrobial peptides has attracted considerable attention in recent years due to the excessive use of antibiotics, which has led to multiresistant bacteria. Cationic amphiphilic Aib-containing peptide models Ac-(Aib-Arg-Aib-Leu)(n)-NH2, n = 1-4, and sequential cationic polypeptides (Arg-X-Gly)(n), X = Ala, Val, Leu, were prepared and studied for their antimicrobial and hemolytic activity, as well as for their proteolytic stability. Ac-(Aib-Arg-Aib-Leu)(n)-NH2, n = 2, 3 and the polypeptide (Arg-Leu-Gly)(n) exhibited significant antimicrobial activity, and they were nontoxic at their MIC values and resistant, in particular the Aib-peptide models, to enzymatic degradation.

Conformational study of new amphipathic alpha-helical peptide models of apoA-I as potential atheroprotective agents.

Aiming at contributing to the development of potential atheroprotective agents, we report on the concept and design of two peptide models, which mimic the amphipathic helices of apoA-I and incorporate Met into their sequences to validate its role as oxidant scavenger: Ac-ESK(Palm)KELSKSW(10)SEM(13)LKEK(Palm)SKS-NH(2) (model 1 [W(10), M(13)]) and Ac-ESK(Palm)KELSKSM(10)SEW(13)LKEK(Palm)SKS-NH(2) (model 2 [M(10), W(13)]). Hydrophobic residues of both models cover about the half of the surface, while the positively and negatively charged residues constitute two separate clusters on the hydrophilic face. Palmitoyl groups were introduced into the Lys-N(epsilon)H(2) groups at positions 3 and 17 to contribute to the amphipathic character of the peptides and stabilize the nonpolar face of the helix.