Disruption of protein phosphatase 1 complexes with the use of bioportides as a novel approach to target sperm motility

Abstract

Endogenous proteomimetic sequences covalently coupled to cell penetrating peptides as sychnologically-organized bioportide constructs were successfully delivered to sperm cells to disrupt protein phosphatase 1 complexes and, consequently, reduce sperm motility.

Efforts to Generate a Male Contraception Just by Prevention of Sperm Motility Acquirement in Epididymis Without Influencing the Physiology of Spermatogenesis: Yet Still a Little Far Goal

“…In caudal sperms, all the 3 inhibitors are bound to PP1γ2 that makes it inactive, whereas in the caput sperm phosphorylation of PPPIR11 avoids the binding of PPPIR7 to PP1γ2 that is thus catalytically active. Depending on these outcomes of Silva et al [7], evaluation of the probable part of PPPIR7 as well as PPPIR11 in the manipulation of sperm motility in men might be the aim of future studies that need to be continued to get more insight in this field. The study performed by Silva et al [7], throws some light on the signaling events which control sperm motility, but still certain unanswered queries need to get tackled in future studies [see figure1].…”

“…Depending on these outcomes of Silva et al [7], evaluation of the probable part of PPPIR7 as well as PPPIR11 in the manipulation of sperm motility in men might be the aim of future studies that need to be continued to get more insight in this field. The study performed by Silva et al [7], throws some light on the signaling events which control sperm motility, but still certain unanswered queries need to get tackled in future studies [see figure1]. It appears too early to talk about the clinical applications of bioportides as male contraceptives in view of their inherent pharmacodynamic as well as pharmacokinetic characteristic that the authors themselves agreed upon [14].…”

“…Recently Silva et al [7], conducted an in vitro study for analyzing the influence of competitive bioportides [used in Cell Penetrating Peptide (CPP) technology] on PP1 activity in addition to human sperm motility with the idea of their proper utilization as newer male contraceptives that target the post testicular sperm maturation along with achieving the motility without any interference in spermatogenesis. In mammals PP1 gets encoded by 3 separate genes that generates PP1α, PP1β as well as PP1γisoforms.…”

“…Nevertheless, sperm motility did not get totally ameliorated by these bioportide fabrications. Thus Silva et al [7], suggested that the combination of utilization of bioportides that were targeting the RVxF-binding area (MSS1) along with the bioportide simulating the unique 22-amino acid C-terminus of PP1γ2 might probably cause a complete finishing of the sperm motility. PPPIR2 represents a markedly intrinsically disarrayed protein that achieves a definite structure only on correlation with PP1 [10].…”

Understanding sperm motility regulation: it’s a long road ahead

“…In the present issue of Fertility and Sterility, Silva et al (3) performed an in vitro study to evaluate the impact of competitive bioportides on both PP1 activity and human sperm motility, in view of their possible use as new male contraceptives targeting posttesticular sperm maturation and acquisition of motility, without affecting spermatogenesis. They designed peptides mimetic of the PP1-binding motif of human AKAP4, a sperm-specific kinase anchor protein previously described as a PP1g2 interactor in human sperm involved in motility regulation, the PP1 binding motif of the human PPP1R2, and the unique 22-amino acid C-terminus of PP1g2, a sperm-specific isoform thought to be the sole responsible for PP1 activity in mammalian sperm.…”