Original article<br><i>In vitro</i> pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?

Aleksandra Tomczyszyn; Balazs Csibrany; Attila Keresztes; Jayapal Reddy Mallareddy; Jolanta Dyniewicz; Aleksandra Misicka; Geza Toth; Andrzej W. Lipkowski

doi:10.5114/fn.2014.47839

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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4/2014
vol. 52

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abstract:

Original article
In vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?

Aleksandra Tomczyszyn

,

Balazs Csibrany

,

Attila Keresztes

,

Jayapal Reddy Mallareddy

,

Jolanta Dyniewicz

,

Aleksandra Misicka

,

Geza Toth

,

Andrzej W. Lipkowski

Folia Neuropathol 2014; 52 (4): 383-393

DOI: https://doi.org/10.5114/fn.2014.47839

Online publish date: 2014/12/30

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AMA

Tomczyszyn A, Csibrany B, Keresztes A, et al. Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?. Folia Neuropathologica. 2014;52(4):383-393. doi:10.5114/fn.2014.47839.

APA

Tomczyszyn, A., Csibrany, B., Keresztes, A., Mallareddy, J., Dyniewicz, J.,  & Misicka, A. et al. (2014). Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?. Folia Neuropathologica, 52(4), 383-393. https://doi.org/10.5114/fn.2014.47839

Chicago

Tomczyszyn, Aleksandra, Balazs Csibrany, Attila Keresztes, Jayapal Reddy Mallareddy, Jolanta Dyniewicz, Aleksandra Misicka,  and Geza Toth et al. 2014. "Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?". Folia Neuropathologica 52 (4): 383-393. doi:10.5114/fn.2014.47839.

Harvard

Tomczyszyn, A., Csibrany, B., Keresztes, A., Mallareddy, J., Dyniewicz, J., Misicka, A., Toth, G.,  and Lipkowski, A. (2014). Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?. Folia Neuropathologica, 52(4), pp.383-393. https://doi.org/10.5114/fn.2014.47839

MLA

Tomczyszyn, Aleksandra et al. "Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?." Folia Neuropathologica, vol. 52, no. 4, 2014, pp. 383-393. doi:10.5114/fn.2014.47839.

Vancouver

Tomczyszyn A, Csibrany B, Keresztes A, Mallareddy J, Dyniewicz J, Misicka A et al. Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?. Folia Neuropathologica. 2014;52(4):383-393. doi:10.5114/fn.2014.47839.

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In the present paper, we report the synthesis, radiolabeling and comprehensive pharmacological evaluation of a C-terminally truncated tachykinin derivative, 3H-KFFGLM-NH2. The C-terminal fragments of endogenous tachykinins are pharmacophores responsible for interaction with the tachykinin receptors NK1, NK2 and NK3. The N-terminal fragments are responsible for modulation of receptor selectivity and interactions with other receptor systems. To evaluate and separate the function of an NK-pharmacophore from the activity of its parent neurokinin, KFFGLM-NH2 was synthesized in both tritiated and unlabeled forms. It has been proposed that the obtained NK-binding profiles of specific reference ligands and KFFGLM-NH2 differentiate monomeric and dimeric forms of NK receptors. We hypothesize that dimers of NK receptors could be specific receptor(s) for C-terminal fragments of all neurokinins as well as their C-terminal fragments, including H-KFFGLM-NH2. Dissociation of dimers into monomers opens access to additional allosteric binding sites. Fully elongated undecapeptide substance P interacts with both the “tachykinin pocket” and the “allosteric pocket” on the monomeric NK1 receptor, resulting in high and selective activation. However, C-terminal hexapeptide fragment analogues, recognizing only the “tachykinin pocket”, may have less specific interactions with all tachykinin receptors in both monomeric and dimeric forms.

keywords:

Original articleIn vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?

Aleksandra Tomczyszyn , Balazs Csibrany , Attila Keresztes , Jayapal Reddy Mallareddy , Jolanta Dyniewicz , Aleksandra Misicka , Geza Toth , Andrzej W. Lipkowski

neurokinin (tachykinin), receptor binding, radioligand, GPCR monomer, dimer, allosteric modulation

Original article
In vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?

Aleksandra Tomczyszyn

,

Balazs Csibrany

,

Attila Keresztes

,

Jayapal Reddy Mallareddy

,

Jolanta Dyniewicz

,

Aleksandra Misicka

,

Geza Toth

,

Andrzej W. Lipkowski