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Chemical Compound Review

D-Leu-Gly     2-[[(2R)-2-amino-4-methyl...

Synonyms: CHEMBL55209, CHEBI:73840, CTK3I8187, AKOS006274107, AC1LT50W, ...
 
 
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Disease relevance of Leu-Gly

  • The effects of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2; MIF) and its three analogs Pro-ILeu-Gly-NHi2, Leu-Gly-NH2 (a metabolite of MIF) and cyclo (Leu-Gly) (an analog derived theoretically from MIF) on tolerance to morphine-induced hyperthermia, hypothermia and catalepsy were studied in male Sprague-Dawley rats [1].
  • Hb Nishinomiya [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]: a novel unstable hemoglobin with reduced oxygen affinity found in a patient with spherocytic hemolysis [2].
  • Since many studies have linked the development of neuroleptic induced tardive dyskinesias with enhanced sensitivity of brain dopamine receptors, and the latter was blocker by cyclo (Leu-Gly), this agent may be of value in preventing the development of symptoms of neuroleptic-induced tardive dyskinesias [3].
  • The ability of Clostridium butyricum cultures to hydrolyze three L-leucine-containing dipeptides (Leu-Leu, Leu-Gly and Gly-Leu) in a synthetic minimal medium is demonstrated by using gas chromatography coupled with mass spectrometry [4].
 

High impact information on Leu-Gly

  • The kcat/KM values for the hydrolysis of both Leu-Gly bonds of cinnamoyl-Leu-Gly-Pro-Leu-Gly-Pro-Leu have been measured for both classes of enzymes [5].
  • In this study, we have determined that the proteolytic processing of FV plasmepsins occurs immediately after a conserved Leu-Gly dipeptidyl motif with uniform kinetics and pH and inhibitor sensitivities [6].
  • They were separated into five groups: Gly and Bns acid; Pro-Leu, Leu-Gly and Leu; Pro; Gly-NH2; and MIF [7].
  • (3) The developmental pattern of activities or peptidases measured with Leu-Gly and Leu-Gly-Gly and of arylamidases measured with Arg- and Arg-Arg-beta-naphthylamides was similar to that of proteinases [8].
  • The neurite outgrowth induced by NGF was inhibited by the dipeptides blocking the ubiquitin mediated proteolysis (Leu-Ala and Leu-Gly) whereas the inactive control dipeptides (Ala-Leu and Ala-His) had no effect [9].
 

Biological context of Leu-Gly

  • The N-terminal amino acid sequence of component II.22.5 was shown to be: Lys-Glu-Gly-Tyr-Ile-Val-Asn-Tyr-His-Thr-Gly-Cys-Lys-Tyr-Thr-Cys-Ala-Lys- Leu-Gly - Asp-Asn-Asp-Tyr-Cys-Leu-Arg-Glu-Cys-Lys- [10].
 

Anatomical context of Leu-Gly

  • Leu-Gly-splitting activity, however, was largely present in the cytosol fraction, with only a small peak in the lysosomal fraction [11].
 

Associations of Leu-Gly with other chemical compounds

  • In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro [12].
  • 1. Two enzymes acting on the linear portion of oxytocin: carboxamidopeptidase (releasing Gly . NH2) and prolyl peptidase (releasing Leu-Gly . NH2) were identified in the cytoplasmic fraction of chicken liver [13].
 

Gene context of Leu-Gly

  • The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant [14].
  • Neuropeptides like TRH, MIF, and cyclo (Leu-Gly) appear to produce similar results although their mechanism of action may be quite different [15].
 

Analytical, diagnostic and therapeutic context of Leu-Gly

  • 3. Daily subcutaneous administration of MIF and cyclo (Leu-Gly) before and during the morphine pellet implantation inhibited the development of tolerance to morphine analgesia [16].
  • Cyclo (Leu-Gly) produces its action on oral administration and, therefore, further studies are warranted with this peptide [15].
  • 5. 3. After differential centrifugation of liver homogenates, Ile-Glu and Leu-Gly-splitting activities were determined in the fractions, under the optimal conditions mentioned above [11].

References

  1. Structure activity relationship studies with hypothalamic peptide hormones. I. Effect of melanotropin release inhibiting factor and analogs on tolerance to morphine in the rat. Bhargava, H.N., Kim, H.S. J. Pharmacol. Exp. Ther. (1982) [Pubmed]
  2. Hb Nishinomiya [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]: a novel unstable hemoglobin with reduced oxygen affinity found in a patient with spherocytic hemolysis. Naito, Y., Takahashi, T., Matsunashi, T., Harano, K., Harano, T. Int. J. Hematol. (2002) [Pubmed]
  3. Inhibition of neuroleptic-induced dopamine receptor supersensitivity by cyclo (Leu-Gly). Bhargava, H.N., Ritzmann, R.F. Pharmacol. Biochem. Behav. (1980) [Pubmed]
  4. Cleavage of L-leucine-containing dipeptides by Clostridium butyricum. Khelifa, N., Brik, M., Tessedre, A.C., De Rocquigny, H., Roques, B.P., Courtieu, J., Rimbault, A. Bioorg. Med. Chem. Lett. (1999) [Pubmed]
  5. Mode of hydrolysis of collagen-like peptides by class I and class II Clostridium histolyticum collagenases: evidence for both endopeptidase and tripeptidylcarboxypeptidase activities. Mookhtiar, K.A., Steinbrink, D.R., Van Wart, H.E. Biochemistry (1985) [Pubmed]
  6. Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum. Banerjee, R., Francis, S.E., Goldberg, D.E. Mol. Biochem. Parasitol. (2003) [Pubmed]
  7. Separation of alkylaminonaphthylenesulfonyl peptides and amin acids by high-performance liquid chromatography. Methods for measuring melanotropin inhibiting factor breakdown. Hui, K.S., Salschutz, M., Davis, B.A., Lajtha, A. J. Chromatogr. (1980) [Pubmed]
  8. Changes in proteolytic enzymes and proteins during maturation of the brain. Marks, N., Stern, F., Lajtha, A. Brain Res. (1975) [Pubmed]
  9. Nerve growth factor induced neurite outgrowth from amphibian neuroepithelial precursor cells is prevented by dipeptides inhibiting ubiquitin-mediated proteolysis. Maufroid, J.P., Bradshaw, R.A., Boilly, B., Hondermarck, H. Int. J. Dev. Biol. (1996) [Pubmed]
  10. Isolation of several toxins from the venom of the scorpion Centruroides limpidus tecomanus Hoffmann. Ramírez, A.N., Gurrola, G.B., Martin, B.M., Possani, L.D. Toxicon (1988) [Pubmed]
  11. Localization and some properties of lysosomal dipeptidases in rat liver. Bouma, J.M., Scheper, A., Duursma, A., Gruber, M. Biochim. Biophys. Acta (1976) [Pubmed]
  12. The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. Janicki, P.K., Gumułka, S.W., Szreniawski, Z., Paulo, E.A., Arnold, Z. Polish journal of pharmacology and pharmacy. (1986) [Pubmed]
  13. Partial purification and characterization of the oxytocin-inactivating enzymes from chicken liver. Brzezińska-Slebodzińska, E., Adamczyk, J. Acta Biochim. Pol. (1979) [Pubmed]
  14. Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. Walter, R. Biochim. Biophys. Acta (1976) [Pubmed]
  15. Drugs that modify opioid tolerance, physical dependence, and abstinence symptoms: preclinical and clinical studies. Bhargava, H.N. NIDA Res. Monogr. (1995) [Pubmed]
  16. The effect of melanotrophin release inhibiting factor (MIF) and cyclo (Leu-Gly) on the tolerance to morphine-induced antinociception in the rat: a dose-response study. Bhargava, H.N. Br. J. Pharmacol. (1981) [Pubmed]
 
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