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Molecular dynamics simulations of conformational behavior of linear RGD peptidomimetics and cyclic prodrugs in aqueous and octane solutions


, : Molecular dynamics simulations of conformational behavior of linear RGD peptidomimetics and cyclic prodrugs in aqueous and octane solutions. Journal of Biomolecular Structure & Dynamics 19(5): 775-788

Conformations available to a class of cyclic prodrugs and corresponding linear RGD peptidomimetics were explored using 1 ns length molecular dynamics simulations performed with the program CHARMM. Water and octane, modeled explicitly, were used as solvents to mimic the change of the environment experienced by the solutes upon partition from water to membrane in the trans-cellular transport process. In water, the linear peptidomimetics tended to populate extended-like structures, characterized by strong favorable interactions with solvent and low intrinsic stability. In these extended conformations the charged termini are able to assume large distances, above 15 ANG for the longest systems. These linear peptidomimetics have been found to exhibit the highest potency in experimental studies, in accord with the trends experimentally observed for RGD peptides. In contrast, in octane compact conformers of the linear peptidomimetics were favored, with all charged groups aggregated and shielded from solvent, exhibiting high intrinsic stability and weak solute-solvent interactions. Our calculations predict a large unfavorable energy change for transferring the linear systems from water to octane, in agreement with experimental findings that these compounds are not transported via the trans-cellular pathway. The cyclic prodrugs did not exhibit major structural differences between the simulations in water and octane, adopting turn-like conformations in both solvents. The limited response of the cyclic structures to changes in the environment leads to energies of transfer from water to octane that are also unfavorable, but much less so than for the linear molecules. This effect is in accord with the observed enhanced passive trans-cellular transport of the cyclic prodrugs.

US$19.90

PMID: 11922835

DOI: 10.1080/07391102.2002.10506784


Other references

Drake, C.G.; Pfalzner, P.M.; Linell, E.A., 1963: Intracavitary Irradiation Of Malignant Brain Tumours. Journal of Neurosurgery 20: 428-434

Fatima, R.; Mathur, S.B.; Neergaard, P., 1974: Importance of Drechslera maydis on seed of crops other than maize. D. maydis [Cochliobolus heterostrophus] was recorded in seeds of watermelon, lettuce, Paspalum scorbiculatum, Phaseolus aureus, P. mungo, sorghum and cowpea, in percentages of 0.3-2.8. The infected seeds were from Ghana, India, Iran and Netherland...

Morano, J.U.; Burkhalter, J.L., 1987: Formation of an undesirable guide wire loop with the Cope introduction set. Cardiovascular and Interventional Radiology 10(2): 109-110

Muntean, W.; Mache, C.J., 1993: Haemophilus influenzae type B (Hib) meningitis in a 14-month-old child despite two vaccinations with Hib conjugate vaccine (PRP-D). Wiener Klinische Wochenschrift 105(18): 523-526

Rudelius, B., 1953: Pulvis carotae ad pilulas; a questionable pill ingredient. Svensk Farmaceutisk Tidskrift 57(9): 170-171

Kalinski, P.; Vieira, P.; Schuitemaker, J.H.N.; Cai, Q.; Kapsenberg, M., 2003: Generation of human type 1- and type 2-polarized dendritic cells from peripheral blood. Methods in Molecular Biology 215: 427-436

Sundsfjord, J.A., 1969: Renal production of agiotensin II. Lancet 2(7624): 807-807

Lemus-Varela, Mía.de.Lourdes.; Arríaga-Dávila, Jé.de.Jesús.; Salinas-López, M.Patricia.; Gómez-Vargas, J.Rafael., 2004: Cardiac tamponade in the neonate as a complication of a central venous catheter. Case report. Central venous access is a necessity for the critically-ill newborn who arrives at a Neonatal Intensive Care Unit; despite being considered a relatively safe procedure, it may cause to complications with fatal consequences. To describe the course...

Gwinner, W.; Plasger, J.; Brandes, R.P.; Kubat, B.; Schulze, M.; Regele, H.; Kerjaschki, D.; Olbricht, C.J.; Koch, K.M., 1998: Passive Heymann-nephritis Central pathophysiological role of xanthine oxidase. Journal of the American Society of Nephrology 9(PROGRAM AND ABSTR ISSUE): 610A-611A, Sept

Lee, S-joo.; Lee, K-Won., 2007: Protective effect of (-)-epigallocatechin gallate against advanced glycation endproducts-induced injury in neuronal cells. Advanced glycation endproducts (AGEs) are believed to be secondary factors in the selective neuronal injury associated with several neurodegenerative disorders. In this study, we investigated the protective effects of (-)-epigallocatechin gallate...