Changes at Position

The conversion of 6-deoxy-2,3-0-isopropyIidene-5-0-toluene- -sul-phonyl-L-maimofuranose (22) into methyl 6-deoxy-2,3-0-isopropylidene-p-D-aUofuranoside (24) with methanolic sodium methoxide was reported by Levene and Compton is) in 1936, but more than twenty years elapsed before an acceptable explanation was produced for the configurational changes at positions 4 and 5. In 1958, Reist et al. proposed that the reaction proceeded with formation of the acyclic epoxide (23), which... 

The mutation that leads to creation of a suppressor tRNA does not always occur in the anticodon. The suppression of UGA nonsense codons generally involves the tRNATlp that normally recognizes UGG. The alteration that allows it to read UGA (and insert Trp residues at these positions) is a G to A change at position 24 (in an arm of the tRNA somewhat removed from the anticodon) this tRNA can now recognize both UGG and UGA. A similar change is found in tRNAs involved in the most common naturally occurring variation in the genetic code (UGA = Trp see Box 27-2). 

These effects are nicely illustrated by changes at position 51.20,21 The tyrosyl-tRNA synthetase from B. stearothermophilus has Thr at this position. The tyrosyl-tRNA synthetase from Bacillus caldotenax differs by just four amino acid residues from that from B. stearothermophilus, but one of the changes is an Ala at position 51 23 The enzyme from E. coli is only 50% identical in sequence but has Pro at... 

Factor XIII SNP G— T in exon 2 causes a Val/Leu change at position 34. The Val34Leu polymorphism increases the rate of thrombin activation of Factor XIII and causes increased and faster clot stabilization (21,22). The Leu34 allele has been shown to play a protective role against arterial and venous thrombosis (23,24). 

The considerable number of meperidine analogs prepared and tested showed that other than ester reversal, changes at position 4 usually abolished or decreased activity. An exception, wherein the ester function was altered to ketone and meta hydroxyl added to the phenyl ring, was ketobemidone (Fig. 5-10D), whose potency over meperidine increased five- to sixfold. However, as with molecular improvements of other opiatelike compounds, addiction liability increased as well. 

From study of the action of invertase on derivatives of sucrose and methyl jS-D-fructofuranoside, it was concluded that small changes at positions 1, or 6 cause loss of enzymic acitivity various azido-, deoxy, and halogenated-derivatives were examined. " ... 

The product of this common mutation is a lysine to glutamate change at position 304 in the mature protein. The K304E mutant was ifound to be unstable in patient fibroblasts and upon overexpression in COS-7 cells, whereas in E. coli most of the protein... 

---