Alanine scan studies

Alanine Scan Studies and Single Amino Acid Replacements. 253... 

Recently, alanine scan studies of the seven most amino-terminal residues in glucose-dependent insulinotropic polypeptide (GIF) were performed to evaluate specific residues fhaf play a role in insulin secretion [90]. Alana et al. could demonstrate the importance of the N-terminus in glucose-dependent insulin release since all analogs, with exception of [Ala ]-GIF, showed reduced or no insulinotropic activity in cultured pancreatic BRIN-BDll cells. 

In addition to the C-terminus, several other regions of Ga have been implicated in receptor binding by a variety of experimental approaches (Fig. 4). Residues in the a4//16 loop contribute to the binding surface as demonstrated by alanine-scanning mutagenesis (Onrust et al, 1997), studies with chimeric Ga proteins (Bae et al., 1997, 1999), sequence analysis of conserved amino acids in Ga subclasses (Lichtarge et al., 1996), chemical cross-linking (Cai et al, 2001), and protection from tryptic proteolysis (Mazzoni and Hamm, 1996). The C-terminal 11 amino acids of Gat and... 

Moreira IS, Fernandes PA, Ramos MJ (2006) Unravelling die importance of protein-protein interaction application of a computational alanine scanning mutagenesis to the study of the IgGl streptococcal protein G (c2 Fragment) complex, J Phys Chem B, 110 10962... 

Systematic SAR studies have provided many receptor antagonists." " A semi-rational approach was used for the discovery of non-peptide antagonists of neuromedin B. The role of each amino acid side chain was defined by alanine scanning in bombesin(7-14)-octapeptide, Ac-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NHj (minimum active fragment), and indicated that Trp , Val " and Leu were most important for the binding affinity to the receptors. A search within the company s compound collection was then initiated for various templates containing Trp, Val/Leu types of... 

The preliminary successes in targeting protein-protein interactions have given rise to an important question What types of PPis are inhibitable A number of studies have focused on predicting the physicochemical properties of small-molecule protein-protein interaction inhibitors, [43 -9] and methods for gauging the inhibitability of protein complexes have been proposed [46]. Jochim and Arora described a computational alanine scanning method to identify helical interfaces in the Protein Data Bank (PDB) [50]. 

Fig. 4.6 Neurokinin receptor agonist. Substance P is a potent NK receptor agonist. After extensive biological studies, the undecapeptide could be truncated to an active hexapeptide with an improved affinity constant of 11.7 nM. To identify the crucial binding position of the hexapeptide, an alanine scan has been performed. The greatest...

Alanine scan, systematic substitution of each amino acid residue of a native peptide by a simple amino acid such as alanine. A first step in structure-activity relationship studies. 

Wilkins DK, Dobson CM, Gross M (2000) Biophysical studies of the development of amyloid fibrils from a peptide fragment of cold shock protein B. Eur J Biochem 267 2609-2616 Williams AD, Shivaprasad S, Wetzel R (2006) Alanine scanning mutagenesis of Abeta(1 0) amyloid fibril stability. J Mol Biol 357 1283-1294... 

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