Conformational restriction of the Tyr53 side-chain in the decapeptide HE.
A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.
Casimir
J R
JR
Laboratoire de Chimie Thérapeutique, Université Claude Bernard, Lyon, France. R.Casimir@ibmc.u-strasbg.fr
Iterbeke
K
K
Van Den Nest
W
W
Trescol-Biémont
M C
MC
Dumortier
H
H
Muller
S
S
Gerlier
D
D
Rabourdin-Combe
C
C
Tourwé
D
D
Paris
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry; D001402:B-Lymphocytes / Q000737:chemistry; D002645:Chickens; D008285:Major Histocompatibility Complex; D051379:Mice; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D013696:Temperature; D014443:Tyrosine / Q000737:chemistry*
D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D010649:Phenylalanine; D009113:Muramidase