Unexpected lability of cysteine acetamidomethyl thiol protecting group Tyrosine ring alkylation and disulfide bond formation upon acidolysis

Cleavage and deprotection of the peptidyl resin H-Asn-Gly-Gly-Cys(Acm)-Glu(OBu^t)-Gln-Tyr(Bu^t)-Cys(Acm)-Ser(Bu^t)-Asp(OBu^t)-[(p-alkoxy)benzyloxy polystyrene resin] using standard conditions with various trifluoroacetic acid-containing mixtures were found to result in partial removal of ordinarily acid-stable S-Acm groups. Thus, apart from the desired peptide H-Asn-Gly-Gly-Cys(Acm)-Glu-Gln-Tyr-Cys(Acm)-Ser-Asp-OH, a disulfide-cyclic peptide derivative was also isolated. Furthermore, it was found that in another major by-product of the peptide resin cleavage the tyrosine side chain had been alkylated with an Acm group in a position ortho to the phenolic function. The formation of both by-products could be suppressed by carrying out the cleavage/deprotection reaction at higher dilution and by inclusion of scavengers such as phenol. An authentic sample of the disulfide-cyclic peptide was obtained by oxidation of H-Asn-Gly-Gly-Cys-Glu-Gln-Tyr-Cys-Ser-Asp-OH using Ellman's reagent. © Munksgaard 1997.     

Temporary Stenting as a Bridge to Surgery

Abrupt occlusion of the coronary artery during PTCA is a relatively common complication. The majority of the acute occlusions occur when there is a significant dissection at the site of the balloon expansion. The use of a temporary stent, which can be expanded and collapsed intraluminally, allowing repositioning and finally removal of the device, is reported in this article.     

Preparation and properties of Nα-Bpoc-amino acid pentafluorophenyl esters

The preparation and properties are reported of several N^x-Bpoc -amino acid pentafluorophenyl esters, including those bearing tert-butyl-, allyl- and trityl-based protecting groups. These derivatives have been used in the solid-phase peptide synthesis of sevral short peptides.     

Orthodromic Pacemaker Circus Movement Tachycardia

We report on the case of a 33-year-old woman with sick sinus syndrome who had an orthodromic pacemaker circus movement tachycardia (PCMT), with antegrade atrioventricular (AV) conduction and a retrograde pathway by means of a DDD (AV universal) pacemaker. This PCMT was provoked and sustained by premature ventricular contraction-synchronous atrial stimulation (PVC-SAS), which is a new feature for the prevention of anti-dromic PCMTs. The conditions for occurrence of this tachycardia were: (1) PVC-SAS; (2) atrial undersensing; (3) first degree AV block. Recommendations for prevention of this pacemaker-mediated tachycardia are given.     

Novel Donor Splice Site Mutation in the KVLQT1 Gene is Associated with Long QT Syndrome

KVLQT1 Gene Mutation and LQTS. Introduction : Inherited long QT syndrome (LQTS) recently has been associated with mutations in genes coding for potassium ( KVLQTI, KCNEI , and HERG ) or sodium ( SCN5A ) ion channels involved in regulating either sodium inward or potassium outward currents of heart cells, resulting in prolongation of the repolarization period. We describe a new mutation, a-1 donor splice site mutation in a kindred with two affected members (QTc = 0.61 and 0.54 sec).
Methods and Results : Single stranded conformation polymorphism (SSCP) analyses were performed on DNA fragments amplified by polymerase chain reaction from DNA extracted from whole blood. Aberrant conformers were analyzed by DNA sequencing. SSCP analysis of the KVLQTI gene revealed an aberrant conformer in the affected family members. DNA sequencing confirmed the presence of a G→A change in the last nucleotide of codon 344. This mutation does not cause an amino acid change, but a change of the splice site characteristics at the 3'end of exon 6. The mutation may affect, through deficient splicing, the putative sixth transmembrane segment of the K⁺ channel, and this type of mutation has not previously been described in KVLQTI.
Conclusion : The clinical course of LQTS in the affected family members, in whom no deaths occurred despite 20 to 30 syncopes, can he explained by the ability of the cellular machinery to perform partial correct splicing in the mutant allele. This type of mutation may be misinterpreted as a normal variant, since it is a point mutation causing neither an amino acid change nor the introduction of a stop codon.