Disease relevance of Cycloglycylglycine

• Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. I. Cell kinetic and biologic effects in cultured L1210, human epidermoid No. 2, and adenocarcinoma 755 cells [1].
• The rhizobacteria Burkholderia cepacia biosynthesized the new tetrapeptide Cyclo[N-(Lys-Phe)-Orn-Val] (1), a 2,5-diketopiperazine, and the known siderophore azurechelin (salicylic acid) [2].

High impact information on Cycloglycylglycine

• Prediction of the estimated human oral absorption (EHOA) using measured lipophilicity (CHI log D) and calculated size (cMR) has allowed us to rank various 2,5-diketopiperazine templates and enabled us to focus effort on those templates with the greatest chance of high bioavailability in humans [3].
• The described sequence of reactions, that is compatible with commonly used protecting moieties for the alpha-carboxy group, cannot be applied to dipeptides, since the cyclization to the six-membered 2,5-diketopiperazine ring occurs preferentially [4].
• Cp2Mo2+-promoted hydrolysis of GSH was followed at pD 7.4 and 5.2 and 40 and 60 degrees C. By contrast, the Cys-Gly bond in [Cp2Mo(Gly-Cys-Gly-S,N)] is cleaved by intramolecular aminolysis at pD > or = 7.4 and 60 degrees C leading to glycine and the Cp2Mo2+ complex of the 2,5-diketopiperazine derivative cyclo-(Gly-Cys) [5].
• All TRH analogs, except diketopiperazine (DKP), were full agonists producing similar maximum stimulation (6.5 +/- 1.1-fold) of [3H]IP production [6].
• The synthesis and evaluation as tryptase inhibitors of a library of 2,5-diketopiperazine derivatives containing guanidine or amidine functional groups is reported [7].

Chemical compound and disease context of Cycloglycylglycine

• 2,5-Piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride (NSC-135758) inhibited DNA synthesis but not RNA and protein synthesis in Adenocarcinoma 755 cells in culture [8].

Biological context of Cycloglycylglycine

• The decomposition kinetics of octyl ester of Gly-Phe (IV) has been investigated at pH 7.4 (37 degrees C) and IV was shown to degrade by first-order kinetics via two parallel pathways (1) intramolecular aminolysis resulting in formation of a 2,5-diketopiperazine and (2) hydrolysis of the ester bond producing the dipeptide [9].
• Experimental results obtained with cultured L1210, human epidermoid No. 2, and Adenocarcinoma 755 cells are consistent in showing that inhibition of proliferation of the cells by 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride is accompanied by cell enlargement [1].

Associations of Cycloglycylglycine with other chemical compounds

• Linear tri- and tetrapeptide precursors of 2,5-piperazinedione were prepared and their conversion to spirocyclic dipeptidase enzymes, the spirocyclic dipeptides (SpDp) were generated from the precursors by a two-step mechanism consisting in the proteolytic release of the C-terminal dipeptide ethyl ester and its subsequent spontaneous cyclization [10].

Gene context of Cycloglycylglycine

• Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor [11].
• Piperazine-2,5-dione was separated from human urine on a C18-column using phosphate buffer-methanol (pH 3.5) as eluent [12].

Analytical, diagnostic and therapeutic context of Cycloglycylglycine

• Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. II. Effects on macromolecular synthesis in cell culture and evidence for alkylating activity [8].

References