PubMed · 3719967
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R M David, Z K Shihabi, M L O'Connor. 1986. Simplified method for cystinuria screening.. https://pubmed.ncbi.nlm.nih.gov/3719967/
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A recently rediscovered reaction of base-assisted lanthionine formation has been applied to several systems of disulfide-bridged peptides. In addition to previously described nonapeptides consisting of i, i+3 cystine linkages, the reaction has now been extended to systems consisting of shorter (i, i+2) and longer (i, i+4) disulfide bridges. The desulfurization reaction is also compatible with disulfide bridges formed through homocysteines and penicillamines, yielding unusual amino acids such as cystathionine and beta,beta-dimethyl lanthionine (referred to as "penthionine") in a peptide chain, respectively. Systematic study of this transformation has provided several new insights into its mechanism. We have observed formation of dehydroalanine and dehydrovaline residues resulting from i, i+2-bridged cysteines and i, i+3-bridged cysteine/penicillamine peptides, respectively, thereby supporting a beta-elimination/Michael-addition mechanism for this transformation. Amino acid analysis and NMR data from total correlation spectroscopy (TOCSY) and (1)H-(13)C heteronuclear single quantum correlation (HSQC) experiments show three diastereomeric lanthionine-bridged peptides in the product mixture. But in the case of desulfurization of a cysteine/homocysteine containing disulfide-bridged peptide, Michael addition appears to be stereoselective, yielding a single stereoisomer of cystathionine within the peptide. According to molecular modeling and CD spectroscopy, constrained peptides such as those containing penicillamine are less likely to undergo facile desulfurization. Flexibility of the torsional angles (C(alpha)H-C(alpha)-C(beta)-S) corresponding to the cysteine residues and temperature appear to be contributing factors determining the extent of desulfurization.
Refining the geometric parameters for the ensemble of conformers, derived earlier in terms of NMR-spectroscopy data for the immunogenic tip of Thailand HIV-1 isolate, was carried out by quantum chemical methods. As a result, (i) the energy characteristics of initial structures were significantly improved, (ii) their relative locations on the scale of formation heats were determined, and (iii) the energy barriers between conformers under study were computed. On the basis of all data obtained, the high resolution 3D structure model, describing the set of stable conformers and containing the biologically active conformation, was proposed for neutralizing epitope of Thailand HIV-1 isolate. The following major conclusions were made based on the analysis of simulated conformations: i) the Gly-Pro-Gly-Gln-Val-Phe stretch forming the immunogenic crown of Thailand HIV-1 isolate exhibits the properties characteristic for metastable oligopeptide that constitutes in solution the dominant structure with other conformations admissible; (ii) three structures out of five NMR-based starting models form the cluster of conformers which adequately describes general conformational features of this functionally important site of gp120; (iii) two structures residing in this cluster are found to be well-ground for implementing the function of immunoreactive conformation of the stretch of interest; (iv) in spite of this observation, the "global" structure which gives rise to inverse gamma-turn in the central Gly-Pro-Gly crest of Thailand HIV-1 gp120 is proposed to be the most probable conformation responsible for the formation of viral antigen-antibody complex in particular case under study.
The reduction-cascade of PETN is described as a combination of cyclic-voltammetric measurements and analytical results together with synthesis of PETN-metabolites; furthermore the electroreduction of pentaerythityldinitrate (PEDN) in the presence and absence of cystine as well as cystine and electrogenerated superoxide-radicalanions to elucidate the interaction of PETN with thiol-species. PETN was recognized as precursor for a initial radicalic process, followed by intermediate formation of pentaerythityltrinitratealdehyde (PENA) inside a self-reducing nitrate-system with NO as final product, which may explain its special position in comparison with other pharmaceutically applied nitratestructures. It could be proved, that a cystine-pool reacts as a selective moderator inside the reduction of PEDN without being interfered by O2.-, yielding pentaerythitylmononitrate (PEMN) meanwhile in the absence of cystine only pentaerythrite (PE) is formed.