• September 26, 2023

What Are Direct Peptides?

Direct peptides (DP) are chemically modified proteins that have formed a bond between the thiol groups of two adjacent peptidyl-cysteine residues. The formation of such bonds can alter protein structure, and in many cases this modification results in the generation of interchain disulfide bridges between cysteines in the protein chain. Disulfide bonds form when the thiol groups on opposite peptidyl-cysteines are reduced and oxidised at alternate times. This chemical oxidation is the molecular initiating event (MIE) of skin sensitisation, as it induces the formation of disulfide bonds between the redox-active cysteine residues that make up the surface of dermal cells and can ultimately lead to the triggering of the inflammatory response known as inflammation.

The DPRA is an OECD test guideline method that was developed to assess the protein reactivity of chemicals that could possibly contribute to the molecular initiating event of skin sensitisation. The DPRA combines incubation of the chemical with the cysteine-rich peptide and fluorescence readout to determine the reactivity parameter logkmax (as per OECD test guideline TG 442C). The reactivity parameters are mathematically analysed to assign the chemicals to either the 1A or the 1B/NC potency class.The DPRA and its recent amendment the DPRA-cys have significant limitations relating to the assumption that potency is solely a function of chemical reactivity alone, i.e. the reactivity-based predictivity performance of these assays. Although the current DPRA data analysis protocol generates kmax values for the DPRA-cys that can be used to assign potency, such numbers cannot with confidence be assumed to represent true second-order rate constants for reaction of the peptide with the chemical, and as such, they are not reliable indices of reactivity. For example, phthalic and trimellitic anhydrides both generate similar kmax values for the DPRA-cys but they can be distinguished in terms of their potency by their differences in hydrophobicity.buy peptides

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