Biomedical subjects
I McEwen
Publications and source records attributed to I McEwen.
NMR and computer-aided modeling studies of the interactions between a cyclic hexapeptide and the two enantiomers of some Boc- and Fmoc-amino acids.
The cyclic hexapeptide cyclo [-Pro1-Gly2-Glu3 (OBzl)-Pro4-Phe5-Leu6-] (1) was modeled and synthesized to be used for chiral discrimination studies. Total correlated spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic hexapeptide 1 in CDCl3 showed the presence of three stereoisomers: two dominant stereoisomers 1a and 1b that exchanged chemically with each other, and a minor stereoisomer 1c (4%) that exchanged exclusively with the stereoisomer 1b. Of the two dominant stereoisomers, only 1a interacted specifically with t-butyloxycarbonyl (Boc-) and 9-flourenylmethyloxycarbonyl (Fmoc-) amino acids in CDCl3. The interaction site of 1a when complexing with the derivatized amino acids was the chain segment Phe5-Leu6. The Phe5 NH and Leu6 NH protons are contiguous and solvent exposed. Their nmr signals shifted strongly downfield with the addition of Boc- or Fmoc- amino acids to the peptide solution. Thus, both NH protons hydrogen bond to the amino acids, forming a two-point hydrogen-bonding complex. The peptide stereoisomer 1b did not interact specifically with the Boc- and Fmoc-amino acids because of the lack of two contiguous and solvent-exposed peptidic NH protons that seem to be needed for specific interactions of the cyclic hexapeptide 1 with the Boc- and Fmoc-amino acids. A clear difference in the interaction of 1a with D- and L-enantiomers of Boc- Trp and Fmoc-Trp was observed with nmr spectroscopy. Docking models and molecular mechanics calculations together with nmr observations showed that the NH proton of the indole ring of the Boc-L-Trp and the Fmoc-L-Trp hydrogen bonded to the Pro1 carbonyl group. In this three-point hydrogen-bonding complex, the indole ring becomes locked underneath the Leu residue. The nmr signals of all the Leu6 protons (except for Leu NH) shifted strongly upfield owing to the shielding effect of the indole aromatic ring currents. The indole NH of the D-enantiomer did not hydrogen bond to the Pro1 carbonyl group because the formation of such a three-point hydrogen-bonding complex was thermodynamically unfavorable.
Formation of several stable complexes between the minor components of the cyclic tetrapeptide cyclo-(-Pro1-Ala2-D-Phe3-Leu4-) and some specific Boc-amino acids.
The cyclic tetrapeptide cyclo (-Pro1-Ala2-D-Phe3-Leu4-) was modeled and synthesized to be used for molecular interactions and chiral discrimination studies in CDCl3. Total correlation spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic tetrapeptide showed the presence of one dominant stereoisomer-1- and three minor ones--2a, 2b, and 2c--in a relationship of 92:6:1:1. They formed three- to five-hydrogen bond complexes with Boc-D-Ser, Boc-L-Ser and Boc-L-Thr (Boc: t-butyloxylcarbonyl). These three Boc-amino acids interact more strongly with 2a, 2b, and 2c than with 1, altering their relative concentrations to 48:40:6:6. In the complex between the cyclic tetrapeptide and Boc-D-Ser, the stereoisomer 2a exchanged chemically with 1, 2b, and 2c, while 1 did not exchange with either 2b or 2c. This chemical exchange is due to cis-trans isomerization of the peptide bonds. The chiral discrimination of 2a, 2b, and 2c was stronger than that of 1. No complexation occurred with Boc-L-Ala or Boc-L-Trp.
Prescriptions for physical and occupational therapy in school.
Prescriptions for occupational and physical therapy in a metropolitan school district are described. Seven physical therapists and 7 occupational therapists completed close-ended questionnaires on 226 prescriptions. An equivalent of 4.5 fulltime therapists did not participate and accounted for 54 other prescriptions. Each prescription was independently reviewed for its form, content, and relative value to therapy. Of all the prescriptions 119 (52%) involved students with cerebral palsy; 35 (15%), diseases or syndromes of the central nervous system; 12 (5%), myelomeningocele; 8 (4%), head trauma; 7 (3%), neuromuscular disorders; and 30 (13%), developmental delay. Of the 226, 210 (93%) involved students enrolled in special educational programs; 108 (48%) of all prescriptions were written on standardized school forms, half of which contained checklists. In 13 (6%), the content was illegible. References made to technique, anatomic site, neurologic, and general terms varied greatly. Fifty-seven (30%) made open or blanket comments for therapy. The dose or intensity of therapy was stipulated in only 5% of cases. Only 15 prescriptions requested feedback. Prescriptions by physiatrists were rated slightly higher than those written by pediatricians and other specialists. It is suggested that the prescription is necessary but not sufficient to assure communication between the physician and the school staff.