Alanylglutamic acid

Objective: To investigate whether perioperative intravenous glutamine supplementation may affect surgical morbidity. Summary background data: Small-sized randomized trials showed a trend toward a reduction of postoperative infections in surgical patients receiving glutamine. Methods: : A randomized, multicentre trial was carried out in 428 subjects who were candidates for elective major gastrointestinal surgery. Inclusion criteria were: documented gastrointestinal cancer, weight loss 18 years. Patients received either intravenous infusion of L-alanine-L-glutamine dipeptide (0.40 g/kg/d; equal to 0.25 g of free glutamine) (Ala-Glu group, n = 212), or no supplementation (control group, n = 216). Glutamine infusion began the day before operation and continued postoperatively for at least 5 days. No postoperative artificial nutrition was allowed unless patients could not adequately eat by day 7. Postoperative morbidity was assessed by independent observers according to a priori definition. Results: Patients were homogenous for baseline and surgical characteristics. Mean percent of weight loss was 1.4 (2.7) in controls and 1.4 (2.4) in Ala-Glu group. Overall postoperative complication rate was 34.9% (74/212) in Ala-Glu and 32.9% (71/216) in control group (P = 0.65). Infectious morbidity was 19.3% (41/212) in Ala-Glu group and 17.1% (37/216) in controls (P = 0.55). The rate of major complications was 7.5% (16/212) in Ala-Glu group and 7.9% (17/216) in controls (P = 0.90). Mean length of hospitalization was 10.2 days (4.8) in Ala-Glu group versus 9.9 days (3.9) in controls (P = 0.90). The rate of patients requiring postoperative artificial nutrition was 13.2% (28/212) in Ala-Glu group and 12.0% (26/216) in controls (P = 0.71). Conclusions: Perioperative glutamine does not affect outcome in well-nourished GI cancer patients.

It is important for ion channel peptides to have energetic stability and ion-selectivity for development of some medicines. In the present study, our objective was to achieve formation of energetically stable and ion-selective channels in the membrane using cyclic tetrapeptides. We succeeded in formation of energetically stable and ion-selective channels using two cyclic tetrapeptides cyclo(D-Ala-Dap)(2) (Dap; l-2,3-diaminopropionic acid) and cyclo(D-Ala-Glu)(2). The results of ion channel recording suggested that the cationic cyclo(D-Ala-Dap)(2) was resulted in Cl(-) anion-selective and the anionic cyclo(D-Ala-Glu)(2) led to K(+) cation-selective ion channel formation, respectively. This ion selectivity may be attributed to the charge state of peptides. And a low-hydrophobic cyclic tetrapeptide; cyclo(D-Ala-Dap)(2) had a tendency to form stable ion channel compared to more high-hydrophobic ones; cyclo(D-Phe-Lys)(2), cyclo(D-Phe-Dap)(2) and cyclo(D-Ala-Lys)(2). Our findings will shed light on the field of ion channel peptide study, especially cyclic one.

The degradation kinetics of five glutamine dipeptides in aqueous solution, i.e. glycyl-L-glutamine (Gly-Gln), L-alanyl-L-glutamine (Ala-Gln), L-valyl-L-glutamine (Val-Gln), L-leucyl-L-glutamine (Leu-Gln) and L-isoleucyl-L-glutamine (Ile-Gln), were studied. Stability tests were performed using a stability-indicating high-performance liquid chromatographic assay. Two different Ala-Gln degradation routes, i.e. the cleavage of a peptide bond and the deamination of an amide group, were observed. The degradation was adequately described by pseudo-first-order kinetics. The maximum stability of Ala-Gln was obtained at an approximate pH of 6.0. The pH-rate profile described by specific acid-base catalysis and hydrolysis by water molecules agreed with the experimental results. The activation energy of Ala-Gln at pH 6.0 was determined to be 27. 1kcal mol-1, and the shelf-life (90% remaining) at 25 and 40 degrees C was predicted to be 5.3 years and 7.1 months, respectively. The rate constants of the glutamine dipeptides were influenced by the N-terminal amino acid residue and decreased in the order: Gly-Gln, Ala-Gln, Leu-Gln, Val-Gln and Ile-Gln.