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Biomedical subjects

G Valencia

Publications and source records attributed to G Valencia.

At least 37 records · Page 2Linked to original sources
PubMed1992

Influence of solvent and water activity on kinetically controlled peptide synthesis.

alpha-Chymotrypsin deposited on Celite was used to catalyse peptide synthesis reactions between N-protected amino acid esters and leucine amide in organic media with low water content. The influence of the solvent and the thermodynamic water activity on the reaction kinetics was studied. The substrate specificity in the reactions was shown to be a combination of the substrate specificity of the enzyme in aqueous media and the influence of the solvents. The magnitude of the solvent effects differed greatly depending on the substrates used. In hydrophobic solvents high reaction rates were observed and the competing hydrolysis of the ester substrate occurred to only a minor extent. Reactions occurred at water activities as low as 0.11, but the rate constants increased with increasing water activity and were about two orders of magnitude higher at the highest water activity tested (0.97).

Animals↗
PubMed1992

Racemization free coupling of peptide segments. Synthesis of an insect neuropeptide.

The total synthesis of the insect neuropeptide derivative Z-Gly-Gly-Ser-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 has been carried out by a convergent solid phase strategy. For the coupling of the N-terminal pentapeptide to the C-terminal tetrapeptide, three different methods were assayed. Racemization of the acyl activated amino acid during the fragment condensation reaction was monitored by HPLC. Best results were obtained by enzymatic coupling in a low water containing media using adsorbed alpha-chymotrypsin. An optically pure product was obtained in 82% yield after 1 h of reaction. Chemical methods such as DIC/HOBt and BOP/HOBt/NMM always rendered highly optically impure products containing 10-20% of the D-epimer.

Amino Acid Sequence↗
PubMed1992

Predictors of cocaine use in pregnancy.

Several hundred thousand infants are exposed to cocaine in utero every year in the United States. In an attempt to provide services for women abusing drugs, various programs have been proposed for prenatal drug testing. This study was conducted to assess the sensitivity, specificity, and predictive values of screening programs based on a variety of clinical and historical factors. Between October 1988 and March 1989, 1111 parturients who delivered at an inner-city hospital had urine samples and data collected. The urine, linked by code number to the data, which contained no identifiers, was tested anonymously for illicit drugs. We then assessed the associations of a variety of historical and clinical variables with positive toxicologies. An acknowledged history of drug use or a combination of no prenatal care and cigarette use provided the most valid prediction of cocaine use, with a 59.8% sensitivity, 97.5% specificity, 70% positive predictive value, and 94.9% negative predictive value for positive urine toxicologic examinations. The addition of clinical data such as low birth weight did not improve predictive values significantly. Although the use of easily available historical data allowed correct identification of 60% of parturients who used cocaine, no combination of factors could detect all users. If it is considered beneficial to identify all users at a given point, then urine toxicology screening would be more appropriate than sole reliance on patient history.

Cocaine↗
PubMed1991

The biologic and social consequences of perinatal cocaine use in an inner-city population: results of an anonymous cross-sectional study.

Cocaine use among pregnant women and reports of its adverse perinatal consequences have increased substantially over the past 10 years. However, most researchers have studied patients registered at drug treatment centers or have relied on voluntary participation by patients, either of which introduces the possibility of selection bias. To determine the frequency and consequences of prenatal cocaine use among an unselected inner-city obstetric population, we collected urine samples from parturient women at a municipal hospital and anonymously tested these specimens for metabolites of cocaine, marijuana, opiates, and methadone. Urine specimens, with linked obstetric data sheets, were available from a study population of 1111 patients, and pediatric data sheets were available for 846 mother-infant pairs. Cocaine metabolites were found in 11.5% of the urine samples collected, whereas metabolites of marijuana, opiates, and methadone, respectively, were present in 1.1%, 1.2%, and 0.3% of the specimens. Cocaine users were more likely than nonusers to have had no prenatal care (51% vs 8.8%; p less than 0.0001), to be American-born rather than Caribbean-born (71% vs 33%; p less than 0.001), and to have a higher parity (1.83 vs 1.14; p less than 0.0001). Infants of cocaine users had a lower mean gestational age (-0.93 weeks; p less than 0.01), a lower mean birth weight (2560 +/- 788 vs 3151 +/- 699 gm; p less than 0.001), and an increased probability of having an Apgar score of less than 7 at 5 minutes (12.5% vs 3.2%; p less than 0.0001). Multiple linear regression analysis that isolated confounding variables such as the presence or absence of prenatal care, maternal age and parity, and the use of cigarettes and alcohol did not substantially affect the differences described above. The effect of cigarette smoking on reducing fetal size was cumulative. In conclusion, cocaine is the most commonly used illicit drug among parturients in this community and is strongly associated with underutilization of prenatal care services. Infants of cocaine users are more likely to be preterm and depressed at birth and to have a low birth weight. Cocaine use, through the above-noted effects, increases the need for prenatal care while simultaneously decreasing the likelihood that it will be obtained.

Adult↗
PubMed1990

A synthetic glycopeptide of substance P analogue (SP6-11) with enhanced NK-1 receptor specificity.

A new glycopeptide analogue of substance P (6-11) (SP6-11), namely, N1,6 (beta-D-glucopyranosyl) [Glu6, Pro9]SP6-11, has been synthesized and found to be water soluble. The in vitro biological activity of this glycopeptide was determined for spasmogenic activity in the guinea pig ileum and for potentiation of electrically evoked contractions in the rat vas deferens. Thus, activities on NK-1, NK-2, and NK-3 receptor types have been differentiated by two assays and, in the case of NK-1 and NK-3, receptors in guinea pig ileum (GPI) were assayed using specific pharmacological procedures. The ED50 values for the analogue and reference peptides substance P (SP), neurokinin A(NKA), and neurokinin B (NKB) were determined and potencies relative to SP were calculated. The analogue is three times more potent than the potent NK-1 agonist SP on NK-1 receptors. Moreover, this glycopeptide proved to be as selective for the NK-1 receptor as the specific agonist SPOMe (the methyl ester of substance P).

Animals↗
PubMed1990

Antinociceptive activity of glycosidic enkephalin analogues.

The antinociceptive activity of two new enkephalin analogues: N1.5-(beta-D-glucopyranosyl)[D-Met2, Pro5]enkephalinamide and N1.5-(beta-D-galactopyranosyl)[D-Met2, Pro5]enkephalinamide was assessed using the tail immersion and paw pressure behavioural tests. Both enkephalin analogues appear to be more active than morphine when injected either into the fourth ventricle or intrathecally; the galactose analogue is more than 5000 times more active than morphine when injected into the fourth ventricle. The analgesic effects produced by the analogues are partially reversed by SC naloxone (0.1 mg/kg) and totally reversed when the dose of naloxone used was 1 mg/kg, suggesting that the analogues act upon more than one type of opiate receptor (mu/delta).

Analgesics↗
PubMed1990

Synthesis and purification of two SP (6-11) analogues with enhanced selectivity for the NK-1 receptor.

Two hexapeptide analogues of Substance P (6-11) have been synthesized. Replacement of Gly9 by proline provides a peptide with tenfold enhanced selectivity for the NK-1 receptor. The corresponding proline-containing glycopeptide incorporating a beta-D-glucopyranosyl residue linked to the side-chain of Glu6 was 100 times more selective than Substance P for the same receptor.

Chemical Phenomena↗
PubMed1989

New glycosylpeptides with high antinociceptive activity.

The antinociceptive activity of two new synthetic glucoside and galactoside enkephalinamide analogues was studied. The effects produced by the new analogues were compared with those obtained with [D-Met2,Hyp5]enkephalinamide and with morphine. The analogues were injected into the fourth ventricle and intrathecally. Tail immersion and paw pressure behavioural tests were used to assess antinociception. One of the analogues studied, O1,5-[beta-D-galactopyranosyl] [D-Met2,Hyp5]enkephalinamide appears to be 57,000 times more potent than morphine.

Analgesics↗
PubMed1989

Synthesis and conformational analysis of a series of galactosyl enkephalin analogues showing high analgesic activity.

Two galactosyl derivatives of [DMet2,Pro5] enkephalin-amide (compound 1), namely [DMet2,Pro5] enkephalin [N1.5-beta-D-galactopyranosyl] amide (compound 2) and O1.5-(beta-D-galactopyranosyl) [DMet2,Hyp5] enkephalin-amide (compound 3) have been synthesized. Such glycosylpeptides have been shown to be extremely potent analgesic agonists. The conformational analysis of these three compounds in DMSO-d6 solution has been carried out using two-dimensional NMR methods. Both the parent compound (1) and the beta N-galactosyl derivative (2) show similar NMR parameters which are consistent with fairly rigid beta-strands at both the N-terminus and C-terminus, connected by a glycine residue that displays a mixture between multiple conformational states. Thus, although the beta N-galactosyl derivative (2) has been shown to be significantly more potent than the parent compound (1) in the tail immersion and paw pressure tests of analgesia, no correlation can be established between the conformation of (1) and (2) in DMSO and the difference in analgesic activity. In contrast, important conformational differences with respect to (1) and (2) have been detected in the beta O-galactosyl derivative (3). In this case, only one of the likely conformations for (1) and (2) are consistent with the experimental data. These data show that the position of the galactose residue in compound (3) causes Gly3 to loose flexibility leading to a more rigid folded conformation. Such a change in conformation could be related to the difference in analgesic activity between (2) and (3).

Amino Acid Sequence↗