Furin is a Ca2+ -dependent serine protease which cleaves proprotein substrates at the Arg-Xaa-(Lys/Arg)-Arg ↓ site to generate biologically active proteins. Furin’s critical role in many cellular events associated with health disorders such as HIV, SARS, anthrax, and influenza as well as cancer has made inhibitors of this enzyme as therapeutic targets. To this date, the most potent inhibitor of furin is the bioengineered serpin (serine protease inhibitors) protein namely α -PDX. It was already demonstrated that the reactive site loop (RSL) of all serpins are prime interactive domains responsible for their protease inhibitory function. Therefore, the objective of the present study was to develop small peptides with the RSL structure of serpin α -PDX, as inhibitors of furin activity. Fifteen peptides were designed from reactive site loop structure of α-PDX (sequences 367-394) with different mutations in this site, and were synthesized using a solid-phase peptide synthesizer, and characterized by MALDI-tof mass spectrometry and amino acid analysis. The inhibitory effects of the designed peptides against furin activity were evaluated by spectroflourometry using QVEGF-C [Abz-QVHSIIRRßSLP-Y(NO2)-A-CONH2, Abz = 2-amino benzoic acid and Y(NO2) = 3-nitro tyrosine] as substrate. The results showed that all of the designed peptides inhibit furin activity with different efficacies in a time and concentration dependent pattern. Peptides containing His or straight alkyl side chain amino acids in positions P2, P3, P6 and P8 have higher efficacy for blocking furin activity in comparison with peptides containing Arg or Lys in that position. The study further revealed that the peptides inactivate furin in a slow tight binding pattern. Our study provides an alternate strategy for development of efficient peptide-based inhibitors of proprotein convertases such as furin.

Primary antibody deficiencies are the most frequent primary immunodeficiency disorders. Bronchiectasis as a feature of these disorders may be developed due to some factors such α-1- antitrypsin deficiency. In order to determine the prevalence of two common α-1-antitrypsin deficiency alleles (PI*Z and PI*S) in Iranian patients with antibody deficiency, this study was performed. The prevalence of PI*M, PI*S, and PI*Z allele combinations was determined in 40 patients with primary antibody deficiency (with and without bronchiectasis) and compared with 60 healthy control subjects. Phenotyping was performed by isoelectric focusing. The phenotype frequencies among patients were as follow: M in 92.5%, S in 2.5% and Z in 5%. There was not any significant difference in distribution of alleles or phenotypes between patients and control subjects. Moreover, no significant difference was found between patients with and without bronchiectasis. We did not find evidence to support an association between α-1-antitrypsin phenotypes and primary antibody deficiencies in a small, controlled study. Larger studies will be required to clarify the relationship between α-1-antitrypsin genotype and susceptibility to bronchiectasis in patients with antibody deficiency.

In a recent article (Int J Endocrinol Metab 8:211-214, 2010), Hashemitabar et al. (1) have shown that intraperitoneal injection of metformin in pregnant mice induces an increase in the levels of Pdx-1 and insulin mRNA in neonatal mice but not in 19.5 embryonic fetuses. On the basis of these results, the authors concluded that metformin affects the regulatory region of the insulin gene only after birth. The transcriptional factor Pdx-1 is expressed in both endocrine and exocrine tissues and is essential for pancreatic development in the embryonic stage (2). Mice with knocked out Pdx-1 gene do not develop a pancreas, therefore, this deletion is lethal (3)...