Evaluation of lactam-bridged neurotensin analogues adjusting ψ(Pro10) close to the experimentally derived bioactive conformation of NT(8-13)

被引：37

作者：

Bittermann, H ^{[1
]}

Einsiedel, J ^{[1
]}

Hübner, H ^{[1
]}

Gmeiner, P ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Emil Fischer Ctr, Dept Med Chem, D-91052 Erlangen, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 22期

关键词：

D O I：

10.1021/jm049644y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a beta-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies showed that the restriction of Psi(Pro(10)) to approximately 130degrees leads to a more than 1000-fold increase of binding affinity for 1 (K-i = 12 nM) when compared to the more flexible analogue [NMeTyr(11)]NT(8-13).

引用

页码：5587 / 5590

页数：4

共 28 条

[1] Novel bioactive and stable neurotensin peptide analogues capable of delivering radiopharmaceuticals and molecular beacons to tumors
Achilefu, S
Srinivasan, A
Schmidt, MA
Jimenez, HN
Bugaj, JE
Erion, JL
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (15) : 3403 - 3411
[2] Identification of residues involved in neurotensin binding and modeling of the agonist binding site in neurotensin receptor 1
Barroso, S
Richard, F
Nicolas-Ethève, D
Reversat, JL
Bernassau, JM
Kitabgi, P
Labbé-Jullié, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) : 328 - 336
[3] Binder EB, 2001, PHARMACOL REV, V53, P453
[4] 1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE
CARPINO, LA
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) : 4397 - 4398
[5] Efficient synthesis of (S)-4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-3-oxo-2H-2-benzazepin-2-acetic acid (Pht-Hba(2,6-Cl2-Bn)-Gly-OH)
Casimir, JR
Tourwé, D
Iterbeke, K
Guichard, G
Briand, JP
[J]. JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (20) : 6487 - 6492
[6] CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[7] PHARMACOLOGICAL AND BIOCHEMICAL PROFILES OF UNIQUE NEUROTENSIN-8-13 ANALOGS EXHIBITING SPECIES SELECTIVITY, STEREOSELECTIVITY, AND SUPERAGONISM
CUSACK, B
MCCORMICK, DJ
PANG, YP
SOUDER, T
GARCIA, R
FAUQ, A
RICHELSON, E
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (31) : 18359 - 18366
[8] In situ generation of Fmoc-amino acid chlorides using bis(trichloromethyl) carbonate and its utilization for difficult couplings in solid-phase peptide synthesis
Falb, E
Yechezkel, T
Salitra, Y
Gilon, C
[J]. JOURNAL OF PEPTIDE RESEARCH, 1999, 53 (05): : 507 - 517
[9] DESIGN, SYNTHESIS, AND CONFORMATIONAL-ANALYSIS OF A NOVEL SPIRO-BICYCLIC SYSTEM AS A TYPE-II BETA-TURN PEPTIDOMIMETIC
GENIN, MJ
JOHNSON, RL
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (23) : 8778 - 8783
[10] SYNTHESIS AND CRYSTAL-STRUCTURE OF A PEPTIDOMIMETIC CONTAINING THE (R)-4.4-SPIRO LACTAM TYPE-II BETA-TURN MIMIC
GENIN, MJ
OJALA, WH
GLEASON, WB
JOHNSON, RL
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (08) : 2334 - 2337

← 1 2 3 →