Octanol–water partition of nonzwitterionic peptides: Predictive power of a molecular size-based model

Buchwald, Péter; Bodor, Nicholas

doi:10.1002/(sici)1097-0134(19980101)30:1<86::aid-prot8>3.0.co;2-i

Cited by 53 publications

(37 citation statements)

References 52 publications

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“…Desde o estabelecimento da Equação de Hansch [1][2][3][4]12 , em 1964, muitos trabalhos têm reconhecido que os efeitos eletrônicos transmitidos por grupos substituintes, não raro, influenciam a atividade biológica de fármacos 11,[22][23][24][25][26][27][28][29] . O entendimento da natureza destes efeitos bem como o seu dimensionamento são de importância fundamental para a compreensão das relações quantitativas entre a estrutura quí-mica e a atividade de compostos bioativos e envolve, necessariamente, o conhecimento da Equação de Hammett 1,3,4,30 .…”

Section: Descritores Estruturais De Caráter Eletrônicounclassified

“…Considerando que o coeficiente de partição é um dos parâmetros físico-químicos mais amplamente utilizado em estudos de QSAR 1,11,19,22,23,42 e que sua determinação é freqüentemente necessá-ria, especialistas optaram por definir um sistema de solventes preferencial para a sua obtenção, embora vários sistemas de solventes possam ser empregados [46][47][48] . Assim, o sistema 1-octanol/tampão fosfato pH 7,4 é considerado o sistema preferencial para a determinação do coeficiente de partição visando sua aplicação em estudo de QSAR.…”

Section: Coeficiente De Partiçãounclassified

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QSAR: a abordagem de Hansch

Tavares¹

2004

Quím. Nova

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Section: Descritores Estruturais De Caráter Eletrônicounclassified

Section: Coeficiente De Partiçãounclassified

QSAR: a abordagem de Hansch

Tavares¹

2004

Quím. Nova

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“…Animal studies clearly show that β-casomorphins opioid-like peptides are derived from β-casein [19][20][21][22][23][24][25][26] . β-Casomorphins are exogenous opioid peptides derivatives containing the common N-terminal amino acid sequence Tyr-Pro-Phe-Pro and have preferential μ-receptor agonistic activity [25] .…”

Section: Discussionmentioning

confidence: 99%

99mTc Bağlı Yeni Bir Peptid: Ratlarda 99m Tc β-Kazomorphin 6 Molekülünün Biyodistrübisyon ve Görüntüleme Çalışması

Ertay¹,

Ünak²,

Eren³

et al. 2016

Kafkas Univ Vet Fak Derg

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Citation of ThisTc β -casomorphin 6, biodistribution and imaging studies on rats. Kafkas Univ Vet Fak Derg, 23, 15-22, 2017. DOI: 10.9775/kvfd.2016 AbstractPeptide radiopharmaceuticals have an increasing significance in nuclear medicine practice. β-casomorphin is a digestive peptide with 6 amino acids (Tyr-Pro-Phe-Pro-Gly-Pro). N terminal amino acid chain mainly tyr-pro-phe-pro structured exogen opioid peptid type beta cosomorphin are μ-receptor agonistic activity with priority. Animal studies show that β-casomorphins can act as opioid receptor agonists. The aim of this study was to label β-casomorphin with 99m Tc and to examine its usefulness as an opioid receptor binding radiopharmaceutical in Albino Wistar rats and cancer cells. β-casomorphin was labeled with 99m Tc radionuclide using bifunctional chelating agent. Quality control studies were done by Instant Thin layer chromatography (ITLC) and High performance liquid chromatography (HPLC) methods. Binding efficiency of the compound was more than 99%. It was observed as stable for at least 3 h at room temperature. Lipophilicity was also performed for labeled molecule. Imaging studies for 99m Tc labeled molecule was done in rats by using gamma camera. For biodistribution studies; 99m Tc labeled molecule was injected to the rats from tail vein and radioactivity per gr weight of each organ was measured as count per second (cps). Receptor specificity was evaluated in imaging and biodistribution studies in experimental animals. Cell labeling studies were also performed on breast and ovarien cancer cells. In terms of evaluating the biodistribution of 99m Tc-β-casomorphin molecule in rats, uterus and ovary displayed high involvement. It was also confirmed by cell labeling studies. If the radiopharmaceutical is radiolabeled with therapeutic radionuclides it would be useful for therapy for uterus, ovary and breast tumors. Keywords Tc β-Kazomorfin 6 Molekülünün Biyodağılım ve Görüntüleme Çalışması ÖzetPeptit radyofarmasötikleri nükleer tıp pratiğinde giderek artan bir öneme sahiptir. β-kazomorfin 6 amino asit (Tyr-Pro-Phe-Pro-GIy-Pro) ile bir sindirim peptitidir. Tyr-Pro-Phe-Pro aminoasit zinciri ile başlayan ekzojen opioid peptid türevi β-kazomorfinler öncelikle μ-resptör agonistik aktiviteye sahiptir. Hayvan çalışmaları β-kazomorfin türevlerinin bir opioid reseptör agonisti olduğunu göstermiştir. Bu çalışmanın amacı, β-kazomorfin'i 99m Tc ile işaretleyerek opioid reseptörler radyofarmasötiği olarak kullanabilirliğini Albino Wistar ratlarda ve kanser hücrelerinde incelemektir. β-kazomorphin bifonksiyonel molekül kullanılarak 99m Tc radyonüklidi ile işaretlendi. Kalite kontrol çalışmaları, ince tabaka kromatografisi (ITLC) ve yüksek performanslı sıvı kromatografisi (HPLC) yöntemleri ile yapıldı. Bileşiğin işaretlenme verimi %99'dan fazla idi. Oda sıcaklığında, en az 3 saat boyunca stabil kaldığı tespit edildi. İşaretli molekülün lipofilite çalışması da gerçekleştirildi. Tc ile işaretli molekülün görüntüleme çalışmaları sıçanlarda gamma kamera kullanılarak gerçekleşti...

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“…G-SFED was applied to predict the octanol-water partition coefficient (log P) of 601 organic compounds (61) and 193 nonzwitterionic peptides (67). Peptide data consist of 185 terminally blocked and eight cyclic neutral peptides of 1-11 amino acids in length.…”

Section: Calculation Of Partition Coefficients Of Organic Compounds Andmentioning

confidence: 99%

A generalized G-SFED continuum solvation free energy calculation model

Lee

Cho

Kang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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An empirical continuum solvation model, solvation free energy density (SFED), has been developed to calculate solvation free energies of a molecule in the most frequently used solvents. A generalized version of the SFED model, generalized-SFED (G-SFED), is proposed here to calculate molecular solvation free energies in virtually any solvent. G-SFED provides an accurate and fast generalized framework without a complicated description of a solution. In the model, the solvation free energy of a solute is represented as a linear combination of empirical functions of the solute properties representing the effects of solute on various solute-solvent interactions, and the complementary solvent effects on these interactions were reflected in the linear expansion coefficients with a few solvent properties. G-SFED works well for a wide range of sizes and polarities of solute molecules in various solvents as shown by a set of 5,753 solvation free energies of diverse combinations of 103 solvents and 890 solutes. Octanol-water partition coefficients of small organic compounds and peptides were calculated with G-SFED with accuracy within 0.4 log unit for each group. The G-SFED computation time depends linearly on the number of nonhydrogen atoms (n) in a molecule, O(n).implicit solvent | macromolecules | linear time A n accurate description of the effect of solvent on solvation is crucial for understanding chemical and biological phenomena. Because many peptide and protein drugs are currently being developed (1, 2), computational efficiency as well as accuracy are very important. Among the different approaches that have been used, continuum solvation models are appealing because of the simplified yet accurate description of the solvent effect (3-8).Continuum solvent models have been developed based on the early work of Born (9), Bell (10), Kirkwood (11), and Onsanger (12). They focus primarily on the description of the solute either at the quantum mechanical level or as a classical collection of point charges and try to represent the influence of the solvent based on an approximate treatment as a dielectric continuum medium. The charge distribution of the solute induces electric polarization of the surrounding solvent, and the electric field generated by the polarized solvent, the reaction field, in turn perturbs the solute, leading to a modification of the charge distribution of the solute. This electrostatic problem of the mutual polarization between solute and solvent can be recast by using boundary conditions at the cavity surface, leading to significant simplifications in the associated equations.In the classical approaches, most work is concerned with describing the electrostatic contribution to the solvation in terms of the Poisson-Boltzmann equation (PBE) (13). Several different computational techniques for solving the PBE have been developed, for example, finite difference methods in which the dielectric property of the solvent is described in terms of a 3D grid around the solute (14-17) and boundary element methods i...

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Octanol–water partition of nonzwitterionic peptides: Predictive power of a molecular size-based model

Cited by 53 publications

References 52 publications

QSAR: a abordagem de Hansch

QSAR: a abordagem de Hansch

99mTc Bağlı Yeni Bir Peptid: Ratlarda 99m Tc β-Kazomorphin 6 Molekülünün Biyodistrübisyon ve Görüntüleme Çalışması

A generalized G-SFED continuum solvation free energy calculation model

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