![]() ![]() Synthetic peptides have been studied for over a century. They can be monitored for diagnostic purposes, such as in the case of C-peptide, which is used to monitor insulin production and to help determine the cause of low blood sugar (hypoglycemia). There is also an increasing number of examples of orally active peptides, which make them more desirable for drug development.Įndogenous peptides have also been utilized for research and medical interventions. Peptides, on the other hand, can often be accessed chemically, and their purification and analysis is much simpler. Further, biologics almost invariable must be injected. Their purification and structural analysis is often complex and expensive. While biologics are often highly safe and effective, they must be produced in bioreactors, which use whole cells. Biological therapeutics, which are generally proteins, have earned an increasing share of the pharmaceutical marketplace over the past few years. Therapeutic peptides also have some advantages compared to their protein counterparts. Peptides' activity can be lengthened by incorporating modifications, such as non-natural and D-amino acids, cyclization and modifications at the N or C-terminus. Not only can peptides be made very selelctive, decreasing the risk of side effects, but they rapidly metabolize by proteases and allow short time activity in the body. More recently, peptides have been considered as the desirable candidates for therapeutics. Researchers' interest in developing peptide ligands and probes for studying target receptors' structures and functions has increased dramatically lately. Peptides' large size and surface area allow for more specific docking to the target molecules. Modern medicinal and biochemical research is unthinkable without peptides application because of their selectivity, specificity and potency interaction with the target proteins. Other organisms have produced peptides as a means for defense, such as fungal production of cyclosporin A used clinically as an immunosuppressant, and cone snail secretion of Ziconotide which is used to treat a pain. They also play a role in endocrine signaling and can act as a growth factor. Peptides are functioning in human body on many ways, such as regulating metabolism (insulin) and mediating pain signals (dynorphin). Peptides often contain up to fifty amino acid residues, protein are molecules with more than fifty amino acid residues. Polymer molecules with ten or fewer amino acid residues are called oligopeptides. The results for a deuterium-labeled peptide indicate that the matrix abstracts a hydrogen atom from either the amide nitrogen or the β-carbon.Ĭα–C bond cleavage MALDI-ISD Nitrogen-centered peptide radical Side-chain loss.Peptides differ from proteins by amount of amino acid residues the molecule contains. radical undergoes hydrogen atom abstraction by the matrix.In addition to the side-chain loss, the resulting a The intense signal arising from d fragments and the lack of or weak signal from a fragments strongly suggest that the C α-C bond cleavage occurs through a nitrogen-centered radical intermediate. According to the calculation of the rate constant, the corresponding fragmentation occurs within 1 ns. The C α-C bond cleavage on the C-terminal side of the carbamidomethylated cysteine residue is found to produce d fragments instead of a fragments. radicals through radical-induced side-chain loss, not from a fragments.To discriminate these processes, I focus on the yield of d fragments, which originate from a In contrast, the dissociation of the β-carbon-centered radical is kinetically feasible under MALDI-ISD conditions, leading to the formation of an a/x The calculations indicate that the nitrogen-centered radical immediately undergoes C α-C bond cleavage, leading to the formation of an a To understand the general mechanism of C α-C bond cleavage by MALDI-ISD, I study the fragmentation of model peptides and investigate the fragment formation pathways using calculations with density functional theory and transition state theory. Nitrogen-centered and β-carbon-centered hydrogen-deficient peptide radicals are considered to be intermediates in the matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD)-induced C α-C bond cleavage of peptide backbones when using an oxidizing matrix. ![]()
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