ABSTRACT
A different approach to the synthesis of dipeptides is described based on the formation of the NHCHR1CONH-CHR2CO bond by carbenoid N-H insertion, rather than the formation of the peptide bond itself. Thus decomposition of triethyl diazophosphonoacetate catalysed by rhodium(II) acetate in the presence of N-protected amino acid amides 8 gives the phosphonates 9. Subsequent Wadsworth-Emmons reaction of 9 with aldehydes in the presence of DBU gives dehydro dipeptides 10. The reaction has been extended to a simple two-step procedure, without the isolation of the intermediate phosphonate, for conversion of a range of amino acid amides 11 into dehydro dipeptides 12 and to an N-methylamide 11 h, and for conversion of a dipeptide to tripeptide (13-->14). Direct conversion, by using methyl diazophenylacetate, of amino acid amides to phenylglycine-containing dipeptides 19 proceeds in good chemical yield, but with poor diastereoselectivity.
Subject(s)
Amides/chemistry , Peptide Biosynthesis , Amino Acids/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry/methods , Spectrophotometry, InfraredABSTRACT
Historically, the pharmaceutical industry has focused on proteins, rather than nucleic acids, as drug targets. But recent advances in the fields of RNA synthesis, structure determination and therapeutic target identification make the systematic exploitation of RNA as a drug target a realistic goal.
Subject(s)
Drug Design , RNA/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents , Antiviral Agents , Binding Sites , Cross-Linking Reagents/metabolism , Crystallography, X-Ray , Ligands , Models, Molecular , Nucleic Acid Conformation , Paromomycin/pharmacology , RNA/chemistry , RNA/genetics , RNA/metabolism , RNA Precursors/chemistry , RNA Precursors/drug effects , RNA Precursors/metabolism , RNA, Fungal/chemistry , RNA, Fungal/drug effects , RNA, Fungal/metabolism , RNA-Binding Proteins/metabolismABSTRACT
The synthesis, antibacterial activities, murine pharmacokinetic and infection model data for a range of aryl and heteroaryl ketone derivatives of monic acid (2a) are reported. The best results were found for the 3-furyl and 2-methoxy thiazol-5-yl analogues.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Mupirocin/analogs & derivatives , Mupirocin/chemistry , Animals , Anti-Bacterial Agents/pharmacokinetics , Humans , Ketones/chemistry , Male , Mice , Mice, Inbred Strains , Microbial Sensitivity Tests , Mupirocin/pharmacology , Sepsis/drug therapy , Staphylococcal Infections/drug therapy , Structure-Activity Relationship , Thiazoles/chemistryABSTRACT
STUDY DESIGN: This investigation measured the immediate effects of 10, 20, and 30 repeated neck retraction movements on the retraction range of motion and resting neck posture in asymptomatic subjects. OBJECTIVES: The results provide baseline gross kinematic data concerning the effects of neck retraction movements. Future work involving patients is anticipated and proposed. SUMMARY OF BACKGROUND INFORMATION: Neck retraction movements are an assessment maneuver and a treatment technique advocated by Robin McKenzie for patients with neck pain. They are a commonly prescribed physical therapy technique used to treat patients with neck pain and dysfunction. No previous studies of this maneuver have been reported. METHODS: Two groups of 15 subjects, one group 20-29 years old and the other 50-59 years old, participated. Each group performed three sets of 10 repeated movements. The position of the head and neck were recorded by the 3Space Isotrak System using markers placed over the spinous processes of selected vertebrae and the tragus of the ear. RESULTS: After the repeated movements, no statistically significant difference was found in neck retraction range of motion, but a statistically significant change in the resting neck posture was detected. CONCLUSIONS: Any changes in neck retraction range of motion observed after the execution of this maneuver in patients with neck pain may be the result of changes in a pathological process. If the postural change were to occur in patients, this treatment maneuver could be beneficial for those attempting to maintain a more retracted neck position for pain relief.
Subject(s)
Cervical Vertebrae/physiology , Adult , Age Factors , Female , Humans , Middle Aged , Movement/physiology , Posture , Reference ValuesABSTRACT
Twenty-five relief admissions for elderly patients with dementia were studied in order to examine the effects of the respite care on the principal carer: 68% of the patients were severely impaired (maximally dependent); 28% markedly impaired (highly dependent). Despite some reservations, carers perceived relief admissions as beneficial to many aspects of their lives and in some cases essential if patients were to remain in the community. It is argued that relief admissions are an essential part of a comprehensive service for patients with dementia in the community.
Subject(s)
Dementia/psychology , Home Nursing/psychology , Program Evaluation , Respite Care/statistics & numerical data , Adult , Aged , Attitude , England , Female , Humans , Male , Middle Aged , Patient Admission , Statistics as Topic , Surveys and QuestionnairesABSTRACT
The instantaneous orientation of a fish can be determined by attaching a magnetic compass sensor to it and then by acoustically telemetering the information to a research vessel's electronic sector scanning sonar. The sensor is housed in a cylindrical capsule with an acoustic transponder to which it is electronically interconnected. Its size and weight are such that it can be fitted to fish of about 40 cm length and above. An operational life of 52 h is obtained from the tag when it is interrogated by the sonar at a consistent rate of 2 pulses s-1. If the rate is reduced by half, the life can be extended to about 68-70 h. Directional accuracy is limited to +/- 22.5 degrees by the physical size of components used in the sensor. Trials of the prototype are described.
