Solubility improvement of an anthrax toxin peptide inhibitor by rational amino acid randomization.
We previously described a potent anthrax toxin inhibitor, based on a phage-library-selected peptide sequence, synthesized as a tetra-branched molecule on a lysine core and further modified for improvement of activity [Pini et al., Biochem. J., 2006, 395, 157]. This branched peptide had very low solubility because of several hydrophobic residues in the peptide sequence. This complicated molecule purification and manufacturing. Here we report a rational modification of the peptide sequence, obtained by construction and selection of several mini libraries of branched peptides, containing sequences randomized in non crucial positions of the original peptide. Mini libraries were screened for solubility and inhibitory activity. This procedure enabled us to obtain a new peptide with a better solubility and identical inhibitory activity.
Pini
Alessandro
A
Dipartimento di Biologia Molecolare, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy. Alessandro Pini pinia@unisi.it
Brunetti
Jlenia
J
Falciani
Chiara
C
Fabbrini
Monica
M
Bracci
Luisa
L
D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D019151:Peptide Library; D010455:Peptides; C030325:anthrax toxin