Novel Technologies for Dipeptide Drugs Design and their Implantation

Abstract

The article is an overview of author’s data obtained in the framework of the project “The Creation of dipeptide preparations” at the V.V. Zakusov Institute of Pharmacology, Moscow, Russia. Advantages of dipeptides over longer peptides consist in that they are orally active owing to higher sta-bility and ability to penetrate biological barriers due to the presence of specific ATP–dependent trans-porters in enterocytes and blood-brain barrier. Two original approaches for dipeptide drugs design have been developed. Both of them are based on the idea of a leading role of central dipeptide fragment of the peptide chain beta-turn in the peptide-receptor interaction. The first approach, named “peptide drug-based design” represents the transformation of known nonpeptide drug into its dipeptide topological analog. The latter usually corresponds to a beta-turn of some regulatory peptide. The second approach represents the design of tripeptoide mimetic of the beta-turn of regulatory peptide or protein. The results of the studies, which led to the discovery of endogenous prototypes of the known non-peptide drugs piracetam and sulpiride, are presented herein. The paper discusses the process, based on the above-mentioned principles, that was used in designing of nontoxic, orally available, highly effective dipeptide drugs: nootropic noopept, dipeptide analog of piracetam; antipsychotic dilept, neurotensin tripeptoid analog; selective anxiolytic GB-115, tripeptoid analog of CCK-4, and potential neuroprotector GK-2, homodimeric dipeptide analog of NGF.

RETRACTED: Noopept; a nootropic dipeptide, modulates persistent inflammation by effecting spinal microglia dependent Brain Derived Neurotropic Factor (BDNF) and pro-BDNF expression throughout apoptotic process

“…The term nootropics (cognition enhancer) is applied to a group of psychoactive substances that stimulate neuronal functions and enhance cognitive performances such as memory [ 23 , 24 ]. N-Phenylacetyl-l-prolylglycine ethyl ester (Noopept), a dipeptide analog of piracetam, is one of these synthesized cognition enhancers [ 25 , 26 ].…”

Analysis of the domestic pharmaceutical market of psychostimulants and nootropic drugs of N06BX group

“…Проте такі діючі речовини з технологічної точки зору характеризуються низькою стабільністю (руйнуються при пероральному застосуванні). Серед штучно синтезованих препаратів пептидної природи також відоме застосування етилового ефіру n-феніл-ацетил-L-пролілгліцину (ноопепту), хімічна структура якого частково подібна до молекули пірацетаму з рецепторним механізмом дії [1].…”

NTS Targeted By miR-182 Modulates the Apoptosis of Goat Endometrial Epithelial Cells

“…Neurotensin (NTS) is a tridecapeptide found in the hypothalamus and the gastrointestinal tract [1]. NTS participates in prenatal metabolism and in the early establishment of the neuronal system [2], and it has been used to design dipeptide drugs with high effectiveness [3]. The development of mam malian preattachment embryos is closely related to apoptosis because abn ormal cells need to be removed [4,5].…”