Mimetic domain

Fig. 22 Photo-crosslinked titin-mimetic hydrogel, with the circles indicating the folded immuno-globulin-like domains and the wavy lines indicating the resilin-like domains. Reproduced from [235] with permission from Nature Publishing Group, copyright 2010...

Luther M, Rusnak D, Sternbach DD, Mehrotra M, Peel M, Shampine L, Davis R, Robbins J, Patel IR, Kassel D, Burkhart W, Moyer M, Bradshaw T, Berman J. Peptide inhibitors of Src SH3-SH2-phosphoprotein interactions. J Biol Chem 1994 269 31711-31719. Also, for pTyr mimics see Ye B, Akamatsu M, Shoelson SE, Wolf G, Giorgetti-Peraldi S, Yan X, Roller PP, Burke TR Jr. L-0-(2-Malonyl)tyrosine a new phosphotyrosyl mimetic for the preparation of Src homology 2 domain inhibitory peptides. J Med Chem 1995 38 4270-4275. 

Stancovic CJ, Plummer MS, Sawyer TK (1997) Peptidomimetic ligands for src homology-2 domains. In Abell A (ed) Advances in amino acid mimetics and peptidomimetics. Jai Press, Greenwich, vol 1, p 127... 

Figures Selective protein modification using a keto amino acid, p-acetyl-L-phenylalanine. (a) Labeling of fluorescein hydrazide to the Z domain protein. Only the mutant protein containing p-acetyl-L-phenylalanine was labeled and became fluorescent, (b) A general method for preparing glycoprotein mimetics with defined glycan structure.

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

Phan, J., Shi, Z-D., Burke, T.R., Jr., and Waugh, D.S. (2005) Crsytal structures of a high-affinity macrocyclic peptide mimetic complex with the Grb2 SH2 domain. J.Mol. Biol. 353,104-115. 

Scheme 5.1.3. Schematic representation of the synthesis of the all-D version of the WW domain of the human peptidyl-prolyl-c/s/tra/is-isomerase Pin 1 by use of substrate mimetics...

Hajduk PJ, Zhou MM, Fesik SW, NMR-based discovery of phosphotyrosine mimetics that bind to the Lck SH2 domain, Bioorg. Med. Chem. Lett., 9 2403-2406, 1999. 

Schmiedeberg N, Schmitt M, Rolz C, Truffault V, Sukopp M, Burgle M, et al. Synthesis, solution structure, and biological evaluation of urokinase type plasminogen activator (uPA)-derived receptor binding domain mimetics. J Med Chem 2002 45(23) 4984 1994. 

Fig. 3. Conformational states for integrins. A-C. Model for a l3 integrin activation, with at least three conformations of the extracellular domain (Takagi et al, 2002). (A) Bent, low affinity conformation. (B) Extended conformation with closed headpiece. (C) Extended conformation with open headpiece shown with bound RGD-mimetic peptide (green CPK). D-H. Model for aiJ3 integrin activation. (D) Bent conformation with low affinity. (E) and (F) with a closed headpiece and closed I domain in...

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