Theoretical grounds and technologies for dipeptide drug development

Two original technologies for dipeptide drug development are described. Both are based on the theoretical idea about major role of the central dipeptide fragment of polypeptide chain β-turn in the peptide–receptor interaction. The first technology named Drug-Based Peptide Design includes movement from the structure of a known non-peptide drug toward its topological peptide analog, usually coinciding with the central region of the β-turn. The other technology represents movement from the β-turn of the regulatory peptide or protein to its dipeptide mimetic. This theoretical view is illustrated by examples of discovery of endogenous peptide prototypes of the well-known non-peptide drugs Piracetam and Sulpiride. The development of highly effective, non-toxic, orally administrable dipeptide drugs such as Noopept and Dilept with nootropic and neuroleptic activities, respectively, as well as dipeptide anxyolytic GB-115 and dipeptide anti-stroke drug candidate GK-2 on the basis of this approach is described.