CONFORMATIONAL SPECIFIC ANTIBODIES (CSA)
We developed 40 antibodies that recognize preferentially GPCRs in the active state both in vitro and in vivo (Gupta et al, J. Biol. Chem. 2007). This method provides a new and powerful technique to examine the duration and extent of activation of endogenous receptors as well as to screen for drugs that are allosteric modulators of family A GPCRs, which are of great potential therapeutic value. The CSA sales are now responsible for 30% of Proteimax net income.
Generation of G-protein coupled receptor antibodies differentially sensitive to conformational states.
Heimann AS, Gupta A, Gomes I, Rayees R, Schlessinger A, Ferro ES, Unterwald EM, Devi LA.
PLoS One. 2017 Nov 1;12(11):e0187306.
Conformation state-sensitive antibodies to G-protein coupled receptors.
Gupta A, Décaillot FM, Gomes I, Tkalych O, Heimann AS, Ferro ES, Devi LA.
J Biol Chem. 2007 Feb 23;282(8):5116-24
Hemopressin is an inverse agonist of CB1 cannabinoid receptors.
Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20588-93.
Peptide 19 (Pep19) induces uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by
the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive- and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications.
The pep19 is the first 100% Proteimax patent and it has passed both in vitro and in vivo the proof of concept phase of product development.
Modified peptide, cb receptor ligand, kit in vitro process for evaluating cb receptor bonds, uses, pharmaceutical composition for modulating cb receptor activity. US 20150291662 A1
A novel peptide that improves metabolic parameters without adverse central nervous system effects.
Sci Rep. 2017 Nov 1;7(1):14781. doi: 10.1038/s41598-017- 13690-9