G-protein coupled receptors (GPCR) tend to desensitize/internalize when exposed to excess agonist.Previously, we have supported the argument that in the case of the oxytocin receptor (OTR), excess agonist (oxytocin, OT) at birth could be implicated with behavioural disorders of the autistic spectrum. In this review, more recent evidence for this hypothesis is summarized, and it is juxtaposed against reports where exogenous OT was found beneficial in alleviating certain undesired behaviours. Facing this dichotomy, we suggest possible in silico drug discovery approaches to mitigate undesired side effect of OT administration/OTR desensitization, especially in the light of potentially emerging agonist therapies. For this, the most important structural features of OTR are reviewed, and we highlight here the need for higher level of theory studies at the easier approachable extracellular receptor side, where loop 3(e3) and the N-terminated strain of OTR appear to offer targets of particular interest for the development of an agent that conditions the action of excess OT. Another approach, based on the development of new agonists with an improved receptor activation to receptor phosphorylation ratio, is also discussed. Finally, the issue of OTR desensitization is put into the broader context of GPCR desensitization and possible implications for behavioural disorders, and the case is made for the usefulness of computational studies in this area.

N-glycosylation is both species and tissue specific with a series of membrane bound glycosidases and glycosyltransferases modifying the oligosaccharide as it moves through the endoplasmic reticulum (ER) and Golgi. Each of these individual enzymatic reactions may not go to completion; therefore giving rise to glycoforms of the polypeptide. Glycosylation patterns of recombinant proteins are relevant for the immunogenicity, the pharmacological activity, pharmacokinetic profile, solubility and stability of the protein. This review describes the effect of primary and the 3-dimensional structure of the protein on sequon occupancy. Heterogeneity due to cell specific glycosylation and tissue culture conditions are discussed with main emphasis on N-glycosylation sequon occupancy. The review also discusses how fully glycosylated with total sequon occupancy glycoproteins which are of prime relevance in the expression of pharmaceutically relevant glycoproteins can be obtained.

Sodium antimony gluconate (SAG) and miltefosine used in the treatment of kala-azar are known to cause several side effects but severe thrombocytopenia has not been reported. Four cases of severe thrombocytopenia, two caused by SAG and two by miltefosine were promptly detected and treated by immediate withdrawal of the offending drugs, platelet and blood transfusions and dexamethasone. After improvement Leishman-Donovan (LD) bodies were demonstrated in splenic aspirates of both patients of SAG group and one of miltefosine and they were treated with 1 mg/kg body wt of amphotericin B for 20 days and cured. One patient of miltefosine group treated outside only on the basis of rK-39 positivity did not show LD bodies in splenic aspirates and improved without any antikala- azar drug. None of the patients relapsed within 6 months of follow up. Prompt detection of side effects under the concept of pharmacovigilance can save life of such patients.