Peptides moieties

Fig. 11. Peptide moiety indicating the monopoles (net charges) on each of the atoms 54 551. This demonstrates that, on the basis of size, charge and accessibility, a polypeptide could more effectively provide selectivity for cations...

In terms of their molecular structures, the nucleotide and protein realms are usually considered to be rather independent of each other. However, these two families of molecules are covalently linked in the translational aminoacyl- RNAs and ribonucleoproteins as well as in the nucleoproteins involved in cellular and viral replication. In these hybrid biomolecules, a (deoxy)ribose phosphate moiety serves as the structural connection between the nucleoside and peptide moieties. 

As in 53 (Scheme 9), the residual peptide sequence C-terminal to pTyr was exchanged against a non-peptide moiety. However, the low affinity of 54 can probably be attributed to an increased flexibility. Comparing 54 with the Grb2-targeted peptidomimetics 41, 42, or 43, it is reasonable to assume that the module C-terminally attached to pTyr in 54 serves as a tripeptide mimetic. 

Nasal Administration. A route that has gained increasing popularity of late for pharmaceutical administration in humans is the intranasal route. The reasons for this popularity are the ease of use (and, therefore, ready patient acceptance and high compliance rate), the high degree and rate of absorption of many substances (reportedly for most substances up to 1000 molecular weight McMartin et al., 1987), and the avoidance of the highly acid environment in the stomach and first-pass metabolism in the liver (particularly important for some of the newer peptide moieties) (Attman and Dittmer, 1971). The only special safety concerns are the potential for irritation of the mucous membrane and the rapid distribution of administered materials to the CNS. 

This review will focus on the use of MCR approaches to cyclic peptides, cyclic peptidomimetics, or cyclic pseudopeptides, including small or medium-sized heterocycles as mimics of peptide motifs and macrocycles with amino acid or peptide moieties. 

Asymmetric reduction of the double bond of the dehydroamino acid residue in 522 can be effected in different ways since the peptide moiety can act as a chiral auxiliary. Heterogeneous hydrogenations using a Pd/C catalyst are the most frequently used conditions. Among the different amino acids evaluated as chiral auxiliaries, proline is the auxiliary of choice and has led to the best diastereodiffer-... 

An analog of the peptido-leukotriene LTD4, in which the peptide moiety has been replaced by cyclo (Gly-Cys) has been synthesized. The requisite cyclodipeptide was made by base-catalyzed cyclization of the linear precursor (Scheme 1) (85TL1951). In this case, the cyclization was achieved at pH 8.5 in aqueous sodium bicarbonate. 

The ergot alkaloids are extensively metabolized in the body. The primary metabolites are hydroxylated in the A ring, and peptide alkaloids are also modified in the peptide moiety. 

Transient IR spectroscopy in the range of the amide I band is a direct tool to follow the structural dynamics of the peptide moiety. IR difference spectra on the bicyclic molecule bc-AMPB are plotted in Fig. 5. Shortly after excitation the absorption is dominated by a red shift. Such a red shift is expected for a strong vibrational excitation of the molecule. On the time-scale of a few picosecond this red shift decays to a large extent and is replaced by a dispersive feature of opposite sign at tD = 20 ps. At later delay times this feature changes details of its shape, it sharpens up and some substructure appears around 1680 cm 1. After 1.7 ns the shape is similar, but not completely identical to the difference spectrum recorded with stationary FTIR spectroscopy. This time dependence shows that the dominant structural change responsible for the IR difference spectrum occurs on the 20 ps time-scale and that minor structural changes continue until nanoseconds and even later times. 

Peptide Moiety of Human-Blood-Group Active Glycoproteins Associated with the ABO and Lewis Groups, Biochem. J. (1969) 115, 125. 

Independently, simple peptide hydroxamic acids (Z-Gly-L-Leu-NHOH and others) were first observed to inhibit the metalloprotease thermolysin in 1977 9,101 The structure was then further improved to the hydroxamidoalkylmalonyl-peptide moiety by considering the substrate specificity of thermolysin and other metalloproteases 10-121 A summary of hydroxamic acids reported to be inhibitors of various metalloenzymes up to 1983 has been published 131 In 1985 hydroxamido-benzylsuccinyl-L-alanine (kelatorphan) was synthesized and found to be one of the best enkephalinase inhibitors 141... 

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