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PubMed1996

Dielectric constant and ionic strength effects on DNA precipitation.

We have investigated the effect of different zwitterionic compounds on DNA precipitation induced by spermine4+. Glycine, beta-alanine, 4-aminobutyric acid, and 6-aminocaproic acid have shown an increasing capacity to attenuate DNA precipitation. This protection effect has been correlated with the dielectric constant increase of their corresponding solutions. Calculations based on these experimental data and counter-ion condensation theory have confirmed the importance of this parameter for DNA-ion interactions and precipitation mechanisms. We have also observed a resolubilization of DNA in the presence of 6-aminocaproic acid at high spermine4+ concentration and in the presence of glycine at high spermidine3+ concentration. This could be explained by an increase of screening effect with polyamine concentration.

Aminocaproic Acid↗
PubMed2001

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (blood from an unrelated donor) blood transfusion. OBJECTIVES: To assess the effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid, and epsilon aminocaproic acid, on peri-operative red blood cell (RBC) transfusion. SEARCH STRATEGY: We searched MEDLINE (to May 1998), EMBASE (to December 1997), web sites of international health technology assessment agencies (to May 1998). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Randomised controlled trials of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: We found 61 trials of aprotinin (7027 participants). Aprotinin reduced the rate of RBC transfusion by a relative 30% (RR=0.70: 95%CI: 0.64 to 0.76). The average absolute risk reduction (ARR) was 20.4% (95%CI: 15.6% to 25.3%). On average, aprotinin use saved 1.1 units of RBC (95%CI: 0.69 to 1.47) in those requiring transfusion. Aprotinin also significantly reduced the need for re-operation due to bleeding (RR=0.40: 95%CI: 0.25 to 0.66). We found 18 trials of tranexamic acid (TXA) (1,342 participants). TXA reduced the rate of RBC transfusion by a relative 34% (RR=0.66: 95%CI: 0.54 to 0.81). This represented an ARR of 17.2% (95%CI: 8.7% to 25.7%). TXA use resulted in a saving of 1.03 units of RBC (95%CI: 0.67 to 1.39) in those requiring transfusion. We found four trials of epsilon aminocaproic acid (EACA) (208 participants). EACA use resulted in a statistically non-significant reduction in RBC transfusion (RR=0.48: 95%CI: 0.19 to 1.19). Comparisons between agents Eight trials made 'head-to-head' comparisons between TXA and aprotinin. There was no significant difference between the two drugs in the rate of RBC transfusion: RR=1.21 (95%CI: 0.83 to 1.76) for TXA compared to aprotinin. Adverse Effects Aprotinin did not seem to be associated with an excess risk of adverse effects, including thrombo-embolic events (thrombosis RR=0.64: 95%CI: 0.31 to 1.31) and renal failure (RR=1.19: 95%CI: 0.79 to 1.79). Fewer data were available for TXA and EACA. REVIEWER'S CONCLUSIONS: From this review it appears that aprotinin reduces the need for red cell transfusion, and the need for re-operation due to bleeding, without serious adverse effects. However, there was significant heterogeneity in trial outcomes, and some evidence of publication bias. Similar trends were seen with TXA and EACA, although the data were rather sparse. The poor evaluation of these latter drugs is unfortunate as results suggest they may be equally as effective as aprotinin, but are significantly cheaper. The evidence reviewed here supports the use of aprotinin in cardiac surgery. Further small trials of this drug are not warranted. Future trials should be large enough to compare the efficacy and cost-effectiveness of aprotinin with that of TXA and EACA.

Aminocaproic Acid↗
PubMed1980

Chemical structure and properties of duck and goose fibrinogen.

Duck and goose fibrinogen were isolated from fresh pooled plasma by three different methods. To minimize proteolytic activity, epsilon-aminocaproic acid and trasylol were used throughout the preparation procedures. Amino acid composition of fibrinogens and carbohydrate content (hexose, hexosamine, sialic acid) as well as phosphorus were analysed. Intact preparations showed single band on SDS-polyacrylamide gel electrophoresis. After reduction and modification of the thiol groups, the material could be separated by SDS-polyacrylamide gel electrophoresis into four bands corresponding to the gamma, partially degraded A alpha, B beta and intact A alpha chain. Intact polypeptide subunits were separated by ion-exchange chromatography or preparative SDS-polyacrylamide gel electrophoresis and their amino acid compositions were determined. Evidences supporting the view that bird fibrinogen is very sensitive to proteolytic degradation and that a partial degradation of the A alpha chain takes place even when inhibitors are used in all steps of the purification procedures are presented.

Amino Acids↗
PubMed1977

Isolation and characterization of native and lower molecular weight forms of sheep plasminogen.

Two major forms of native sheep plasminogen (SPg-a) have been isolated from plasma by affinity chromatography. These forms differ in molecular weight, charge characteristics, affinity for epsilon-aminocaproic acid (epsilon-Ahx), and carbohydrate content. Upon treatment of SPg-a with plasmin, lower molecular weight plasminogens can be isolated. A plasminogen (SPg-b) of molecular weight approximately 8,000 less than native plasminogen is rapidly produced when either major plasminogen form is treated with plasmin. The molecular weight differences found in the major SPg-a forms are retained in the SPg-b forms, derived from each SPg-a. Upon protracted treatment of either major form of SPg-a or SPg-b with plasmin, a plasminogen (SPg-c) or molecular weight approximately 32,000 less than SPg-b is produced. A single peptide (P) is also produced in this step. The SPg-c species produced from each original SPg-a major form possess essentially the same molecular weights and carbohydrate compositions; but the P cleaved retains the molecular weight and carbohydrate differences found in each major SPg-a or SPg-b form. A large decrease in the S20,w of SPg-a is observed upon the binding of epsilon-Ahx to this protein. A much smaller alteration in the S20,w of SPg-b and SPg-c is observed upon binding of epsilon-Ahx to these proteins.

Amino Acids↗
PubMed1968

Activity of homocarnosine and other compounds against staphylococcal infections in mice.

Homocarnosine and carnosine have been identified in bovine brain extracts which are effective in protecting mice against infections by Staphylococcus aureus. These peptides, as well as l-1-methylhistidine, beta-alanine, gamma-aminobutyric acid, delta-aminovaleric acid, epsilon-aminocaproic acid, 1-aminomethylcyclohexane-4-carboxylic acid, and anserine, were tested as prophylactic agents against S. aureus infections in C3H and Swiss mice. Histidine and methylhistidine were ineffective in preventing mortality in both mouse strains. Carnosine, anserine, and epsilon-aminocaproic acid were effective in C3H but not in Swiss mice. beta-Alanine and gamma-aminobutyric acid were weakly effective (C3H) or ineffective (Swiss). delta-Aminovaleric and 1-aminomethylcyclohexane-4-carboxylic acid (tested only in Swiss) were somewhat effective in early stages of the infection. Homocarnosine was the best compound and was highly effective in protecting both mouse strains against S. aureus infections by the testing procedure employed.

Alanine↗
PubMed2006

Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial.

BACKGROUND: Risks and costs of allogeneic blood transfusions mandate strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement. METHODS: A double-blind, randomized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement. Patients in the study group received tranexamic acid 10 mg kg(-1) i.v. just before the tourniquet was deflated and 3 h later, or epsilon-aminocaproic acid 100 mg kg(-1) before tourniquet deflation followed by continuous perfusion (1 g h(-1)) during 3 h. External perioperative blood loss was measured and total blood loss was calculated. The number of patients transfused and number of packed red cell (PRC) units transfused was recorded and possible postoperative thromboembolic complications were investigated. RESULTS: Total blood loss [mean (sd)] was 1099 ml (535) in the group that received antifibrinolytic agents and 1784 ml (660) in the control group (P<0.001). Five patients (7.5%) in the study group and 23 (38.3%) in the control group (P<0.001) received blood transfusions; the first group received a mean of 0.10 PRC unit per patient and the second, 0.58 (P<0.001). Mean reduction in haemoglobin levels (g dl(-1)) between preoperative and fifth day postoperative readings was 2.5 (0.9) in the study group and 3.4 (1.2) in the control group (P<0.001). Clinical assessment did not reveal any thromboembolic complications. CONCLUSIONS: Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement, reflected in a reduction in the number of blood transfusions required.

Aged↗
PubMed1995

epsilon-Aminocaproic acid-associated myopathy in a child.

PURPOSE: A 12-year-old girl developed severe autoimmune thrombocytopenia after a bone marrow transplant for acute lymphoblastic leukemia. RESULTS: Although epsilon-aminocaproic acid helped to control her bleeding, it eventually caused a rare myopathy previously undescribed in a pediatric patient. CONCLUSION: The myopathy resolved when the drug was discontinued and a different antifibrinolytic agent was used.

Aminocaproic Acid↗
PubMed1965

STUDIES ON THE TISSUE ACTIVATOR OF PLASMINOGEN. DISTRIBUTION OF ACTIVATOR AND PROTEOLYTIC ACTIVITY IN THE SUBCELLULAR FRACTIONS OF RABBIT KIDNEY.

1. On subcellular fractionation of rabbit kidney by differential and density-gradient centrifugation, a high proportion of the tissue activator of plasminogen activity was found to be particulate and displayed sedimentation properties associated with the lysosome-rich fraction as judged biochemically by the acid-phosphatase activity. 2. The activator activity is closely associated with a latent protease whose activity is enhanced in the presence of Triton X-100 or sodium deoxycholate in the neutral pH range. Besides hydrolysing casein this protease is also capable of attacking fibrinogen at pH7.4. 3. The pH optimum for activator activity and its inhibition by in-hexanoic acid (in-aminocaproic acid) point to its possible similarity to urokinase, an activator of plasminogen present in the urine of most mammals.

Acid Phosphatase↗
PubMed2001

Effect of progressive benzyl substitution on the conformations of aminocaproic acid-cyclized dipeptides.

The constraint of dipeptides into a beta-turn conformation can be accomplished by linking the two ends of a standard dipeptide with a linker derived from aminocaproic acid (Aca). To elucidate the possibility of using substituted Aca linkers in peptidomimetic design, a series of five macrocycles composed of a monobenzylated Aca linker (containing the benzyl group on each of the five methylene groups of the parent linker) and Gly-Gly were synthesized. The requisite linkers were made by regiochemically controlled ring expansion techniques (for substitution on Aca positions C-3, C-4, or C-5), an Evans alkylation route (for C-2), or by chain extension of L-phenylalanal (for C-6). The solution-phase conformations of the macrocycles were examined by NMR and CD techniques; in addition, crystal structures of the C-4- and C-6-benzyl-substituted linkers were obtained. Four out of the five macrocycles were found to exist with the dipeptide portion taking up either a type II or II' beta-turn conformation, but the Gly-Gly unit in the compound derived from 4-benzyl-Aca did not correspond to one of the standard beta-turn types.

Aminocaproic Acid↗
PubMed2002

Increase of sample load without peak deterioration by careful selection of electrolyte in capillary zone electrophoresis.

In this study it is demonstrated that much higher concentrations of bases dissolved in water can be injected in capillary zone electrophoresis without causing peak deterioration, e.g., peak splitting, if it is the co-ion that buffers instead of the counter-ion. Those findings can be utilised to control peak shapes and in this way an increase in the sample load and indirectly a decrease in the detection limits of impurities in the sample can be obtained. Good results were obtained with 4-aminobutyric and 6-aminocaproic acids as buffering co-ions. Another possibility evaluated successfully was that of using a dibasic acid, malic acid or succinic acid. With an electrolyte containing both succinic acid and 6-aminocaproic acid at pH 4.5, it was possible to load at least 10-20 times more of the test substances imidazole, creatinine or 2-aminopyrimidine dissolved in water than with an electrolyte at the same pH containing acetic acid and tris(hydroxymethyl)aminomethane.

Electrolytes↗
PubMed2004

[Therapeutic approach of hereditary angioedema].

PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH). Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families) with HAE and their evolution. METHODS: Ten patients (1-38 years old) with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50) for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10); low serum C4 level (8/10); undetectable CH50 (3/10) and low CH50 levels (6/10); low APH50 levels (2/10). Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although HAE is caused by the same defect and affects members of the same family, various approaches have been taken to treat these patients. We observed different alternatives of prophylactic therapy for HAE, of which some did not require drug therapy.

Adolescent↗
PubMed1987

The control of the urokinase-catalyzed activation of human glutamic acid 1-plasminogen by positive and negative effectors.

The urokinase-catalyzed activation of human Glu1-plasminogen (Glu1Pg) has been found to be inhibited by monovalent anions in the following order of effectiveness: I- greater than SCN- greater than Cl- greater than IO3- greater than HCOO- greater than F- greater than OAc-. The inhibition is reversed by epsilon-aminocaproic acid, with its effectiveness in this capacity generally inversely proportional to the strength of the binding of the anion. The physical basis for the anion inhibition and epsilon-aminocaproic acid stimulation lies in the ability of these effectors to cause measurable opposite alterations in the conformation of Glu1Pg, which are revealed through study of the sedimentation velocity of the protein under various conditions. The kinetic mechanism of the chloride inhibition of Glu1Pg activation has been examined in detail. It has been found that the Glu1Pg.Cl complex serves as an alternate substrate to Glu1Pg for urokinase, with a greatly increased Km (25 +/- 3 and 2.2 +/- 0.3 microM, respectively) for activation. The kcat for the urokinase.Glu1Pg.Cl complex is approximately the same as that for urokinase.Glu1Pg (1.6 +/- 0.2 - 2.0 +/- 0.2/s). Similarly, the stimulation by epsilon-aminocaproic acid also results from effects on the Km of the activation, which is reduced to 1.8 +/- 0.2 microM for the Glu1Pg.Cl.epsilon-aminocaproic acid complex. The kcat for the urokinase.Glu1Pg.Cl.epsilon-aminocaproic acid of 2.4 +/- 0.3/s complex is not greatly different from that for urokinase.Glu1Pg.Cl. Nuclear magnetic resonance studies of the Glu1Pg-induced line broadening of the 35Cl- spectra in the presence and absence of epsilon-aminocaproic acid suggest that Cl- and epsilon-aminocaproic acid simultaneously bind to the protein and that each of these effectors displays its effects through separate binding sites.

Anions↗
PubMed1995

Aprotinin reduces the need for blood products during liver transplantation.

BACKGROUND: Bleeding complications and blood product consumption have been a major concern during liver transplantation. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood-product consumption. PATIENTS AND METHODS: Use of blood-products (packed red cells, frozen plasma, platelets, and cryoprecipitate) was analyzed both during the three stages of orthotopic liver transplantation and during total hospitalization of the 26 patients transplanted without aprotinin and the subsequent 40 patients with aprotinin. A similar analysis was performed for 15 patients immediately before and after the introduction of aprotinin to eliminate the "learning curve" effect for liver transplantation. The effect of epsilon-amino-caproic acid was analyzed as 13 patients received neither epsilon-aminocaproic acid nor aprotinin and 13 patients received epsilon-aminocaproic acid but not aprotinin. RESULTS: There was a significant reduction in total hospital use of cryoprecipitate, frozen plasma, platelets, and red cells in the aprotinin-treated patients. This reduction was seen during the anhepatic and reperfusion stages of liver transplantation. There was no difference in blood product consumption between the groups who were or were not treated with epsilon-aminocaproic acid. CONCLUSION: Aprotinin significantly reduces the need for red cell, frozen plasma, platelet, and cryoprecipitate transfusion use during orthotopic liver transplantation, and appears to be more efficacious than epsilon-aminocaproic acid.

Adolescent↗
PubMed2001

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

OBJECTIVE: To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. DATA EXTRACTION: The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. DATA SYNTHESIS: Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. CONCLUSIONS: Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

Aminocaproates↗
PubMed1995

Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs.

Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted.

Adult↗
PubMed1989

Effect of plasmin inhibitors on gastric mucosal permeability in rats.

We examined the protective effect of plasmin inhibitors on gastric mucosal vascular permeability in rats. Tranexamic acid and aminocaproic acid significantly inhibited the increase in vascular permeability and macroscopic gastric mucosal lesions induced by 50% ethanol and 1% ammonia. The protective effect afforded by plasmin inhibitors was not affected by pretreatment with indomethacin. Our results show that plasmin inhibitors inhibit the increase in gastric vascular permeability and suggest that plasmin may play an important role in the pathogenesis of gastric mucosal damage.

Aminocaproates↗
PubMed1975

Studies on convulsants in the isolated frog spinal cord. I. Antagonism of amino acid responses.

1. The isolated frog spinal cord was used to study the effects of picrotoxin, bicuculline, and strychnine on the responses of primary afferents to amino acids. Recording was by sucrose gap technique. 2. A series of neutral amino acids was found to depolarize primary afferents. Optimal activity was obtained by an amino acid whose carboxyl and amino groups were separated by a three-carbon chain length (i.e. GABA). Amino acids with shorter (i.e. beta-alanine, glycine) or longer (i.e. delta-aminovaleric acid, epsilon-aminocaproic acid) distances between the charged groups were less potent. Imidazoleacetic acid was the most potent depolarizing agent tested. 3. Picrotoxin and bicuculline antagonized the primary afferent depolarizations of a number of amino acids tested with equal specificity. Depolarizing responses to standard (10- minus 3 M) concentrations of beta-alanine and taurine were completely blocked by these convulsants, while depolarizations to 10- minus 3 gamma-aminobutyric acid (GABA) were only partially antagonized. Glycine responses were unaffected by these agentsk; Strychnine completely blocked beta-alanine and taurine depolarizations and incompletely antagonized several other neutral amino acids. GABA, glutamate, and glycine depolarizations were not affected. 5. These results suggest that there are at least three distinct populations of neutral amino acid receptors on primary afferent terminals: a GABA-like receptor, a taurine/beta-alanine receptor, and a glycine-like receptor. The strychnine resistance of the glycine responses indictaes that the primary afferent receptors for glycine differ from those on the somata of spinal neurones.

Alanine↗
PubMed2000

Reactivity toward deamidation of asparagine residues in beta-turn structures.

Mimetics of beta-turn structures in proteins have been used to calibrate the relative reactivities toward deamidation of asparagine residues in the two central positions of a beta-turn and in a random coil. N-Acetyl-Asn-Gly-6-aminocaproic acid, an acyclic analog of a beta-turn mimic undergoes deamidation of the asparaginyl residue through a succinimide intermediate to generate N-acetyl-Asp-N-Gly-6-aminocaproic acid (6-aminocaproic acid, hereafter Aca) and N-acetyl-L-iso-aspartyl (isoAsp)-Gly-Aca (pH 8.8, 37 degrees C) approximately 3-fold faster than does the cyclic beta-turn mimic cyclo-[L-Asn-Gly-Aca] with asparagine at position 2 of the beta-turn. The latter compound, in turn, undergoes deamidation approximately 30-fold faster than its positional isomer cyclo-[Gly-Asn-Aca] with asparagine at position 3 of the beta-turn. Both cyclic peptides assume predominantly beta-turn structures in solution, as demonstrated by NMR and circular dichroism characterization. The open-chain compound and its isomer N-acetyl-Gly-Asn-Aca assume predominantly random coil structures. The latter isomer undergoes deamidation 2-fold slower than the former. Thus the order of reactivity toward deamidation is: asparagine in a random coil approximately 3x(asparagine) in position 2 of a beta-turn approximately 30x (asparagine) in position 3 of a beta-turn.

Amino Acid Sequence↗