Modified synthesis and binding properties of a peptide receptor

Tetrahedron Letters

Volumn 38, Issue 6, 1997, Pages 1095-1098

  Dowden, James ^a   Edwards, Peter D ^b   Kilburn, Jeremy D ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDE; MACROCYCLIC COMPOUND; RECEPTOR;

ARTICLE; BINDING AFFINITY; DRUG SYNTHESIS; ENANTIOMER; IN VITRO STUDY; MODEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RECEPTOR BINDING; STRUCTURE ACTIVITY RELATION;

EID: 0031562063     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00068-3     Document Type: Article

References (13)

1. 1. Flack, S. S.; Kilburn, J. D. Tetrahedron Lett., 1995, 36, 3409.
2. 2. Stille, J. K. Angew. Chem., Int. Ed. Engl., 1986, 25, 508.
3. 3. Azizian, H.; Eaborn, C.; Pidcock, A. J. Organomet. Chem., 1981, 215, 49.
4. 4. Bertho, J.-N.; Loffet, A.; Pinel, C.; Reutter, F; Sennyey, G. Tetrahedron Lett., 1991, 32, 1303.
5. 5. The binding data was analysed using Wilcox's Hostest 5 software (Wilcox, C. S.; Glagovich, N. M. University of Pittsburgh, USA, © C. S. Wilcox and the University of Pittsburgh, 1993.). Errors were estimated by averaging data from several titration experiments and by applying the error analysis provided by the Hostest software. In general the titration data showed a very good fit for assumed 1:1 binding. Neither the macrocycle nor the substrates appear to dimerise or aggregate to an appreciable extent at the concentrations used in these titrations as adjudged by simple dilution experiments.
6. 6. Walsh, C. T.; Fisher, S. L.; Park, I.-S.; Prahalad, M.; Wu, Z. Chemistry and Biology, 1996, 3, 21.
7. 7. Dancer, R. J.; Try, A. C.; Sharman, G. J.; Williams, D. H. J. Chem. Soc., Chem. Commun., 1996, 1445.
8. 8. See for example Yoon, S. S.; Still, W. C. Tetrahedron 1995, 51, 567; Gennari, C.; Nestler, H. P.; Salom, B; Still, W. C. Angew. Chem. Int. Ed. Eng., 1995, 34, 1765; Waymark, C. P.; Kilburn, J D; Gillies, I Tetrahedron Lett, 1995, 36, 3051.
9. 8. See for example Yoon, S. S.; Still, W. C. Tetrahedron 1995, 51, 567; Gennari, C.; Nestler, H. P.; Salom, B; Still, W. C. Angew. Chem. Int. Ed. Eng., 1995, 34, 1765; Waymark, C. P.; Kilburn, J D; Gillies, I Tetrahedron Lett, 1995, 36, 3051.
10. 8. See for example Yoon, S. S.; Still, W. C. Tetrahedron 1995, 51, 567; Gennari, C.; Nestler, H. P.; Salom, B; Still, W. C. Angew. Chem. Int. Ed. Eng., 1995, 34, 1765; Waymark, C. P.; Kilburn, J D; Gillies, I Tetrahedron Lett, 1995, 36, 3051.
11. 9. Molecular modelling was carried out using Macromodel V5.0 (Mohamadi, F.; Richards, N.G.J.; Guida, W.C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W.C. J. Comput. Chem. 1990, 11, 440) on a Silicon Graphics workstation. The AMBER* parameters (Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765) were used and solvent was included using the GB/SA continuum model of chloroform (Still, W.C.; Tempczyk, A.; Hawley, R.C. J. Am. Chem. Soc. 1990, 112, 6127). A range of geometries were determined for the free macrocycle and for the complex with the dipeptide N-Cbz β-alanyl-L-alanine by successive simulated annealing molecular dynamic simulations.
12. 9. Molecular modelling was carried out using Macromodel V5.0 (Mohamadi, F.; Richards, N.G.J.; Guida, W.C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W.C. J. Comput. Chem. 1990, 11, 440) on a Silicon Graphics workstation. The AMBER* parameters (Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765) were used and solvent was included using the GB/SA continuum model of chloroform (Still, W.C.; Tempczyk, A.; Hawley, R.C. J. Am. Chem. Soc. 1990, 112, 6127). A range of geometries were determined for the free macrocycle and for the complex with the dipeptide N-Cbz β-alanyl-L-alanine by successive simulated annealing molecular dynamic simulations.
13. 9. Molecular modelling was carried out using Macromodel V5.0 (Mohamadi, F.; Richards, N.G.J.; Guida, W.C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W.C. J. Comput. Chem. 1990, 11, 440) on a Silicon Graphics workstation. The AMBER* parameters (Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765) were used and solvent was included using the GB/SA continuum model of chloroform (Still, W.C.; Tempczyk, A.; Hawley, R.C. J. Am. Chem. Soc. 1990, 112, 6127). A range of geometries were determined for the free macrocycle and for the complex with the dipeptide N-Cbz β-alanyl-L-alanine by successive simulated annealing molecular dynamic simulations.