Gareth Wyn Roberts

Specific Interactions Between Sense and Complementary Peptides: The Basis for the Proteomic Code

After the publication of the review, the authors would also like to offer the following provisional definition of the proteomic code as an aid to discussion: The proteomic code can be provisionally defined as strategic pairs of amino acid residues that make specific contact/interactions with each other through space. These strategic pairs may correspond to M-I pairs in the first instance (specified by the genetic code and its complement) or to M-I pair derivatives thereof. Table 3. Table to show how the Root-Bernstein (R-B) pairs of amino acid residues are derived.

Inhibition of β‐Amyloid Aggregation and Neurotoxicity by Complementary (Antisense) Peptides

Complementary peptides are coded for by the nucleotide sequence (read 5′→3′) of the complementary strand of DNA. By reading the sequence of complementary DNA in the 3′→5′ direction, alternative complementary peptides may be derived. We describe the derivation, testing and analysis of six complementary peptides designed against β‐amyloid peptide 1‐40 (Aβ1‐40). Data is presented to show that one peptide, designated 3′→5′ βCP1‐15, binds specifically to Aβ1‐40, and inhibits both fibrilisation and neurotoxicity in vitro. This suggests that complementary peptides could be useful leads for drug discovery, especially where diseases of protein misfolding are concerned.

Mechanistic Investigation into Complementary (Antisense) Peptide Mini-Receptor Inhibitors of Cytokine Interleukin-1

Sense peptides are coded for by the nucleotide sequence (read 5′→3′) of the sense (positive) strand of DNA. Conversely, a complementary peptide is coded for by the nucleotide sequence (read 5′→3′) of the complementary or antisense (negative) strand of DNA. In many instances, sense and corresponding complementary peptides have been observed to interact specifically. In order to study this process in more detail, longer, shorter and mutant variants of our original complementary peptide, VITFFSL, were synthesised and analysed for binding to and inhibition of cytokine human interleukin‐1β (IL‐1β) in vitro. The behaviour of all peptides studied is discussed in terms of the Mekler–Idlis (M‐I) pair theory, a theory that accounts for specific sense–complementary peptide interactions in terms of through‐space interactions between corresponding pairs of amino acid residues (M‐I pairs)] specified by the genetic code and its complement.