Protamine

Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization.

They may allow for denser packaging of DNA in the spermatozoon than histones, but they must be decompressed before the genetic data can be used for protein synthesis.

However, part of the sperm's genome is packaged by histones (10-15% in humans and other primates) thought to bind genes that are essential for early embryonic development.

[4] Before the toroid is formed, histones are removed from the DNA by transition nuclear proteins, so that protamine can condense it.

The effects of this change are 1) an increase in sperm hydrodynamics for better flow through liquids by reducing the head size 2) decrease in the occurrence of DNA damage 3) removal of the epigenetic markers that occur with histone modifications.

[10] A chain shortened version of protamine also acts as a potent heparin antagonist, but with markedly reduced antigenicity.

It was initially produced as a mixture made by thermolysin digestion of protamine,[11] but the actual effective peptide portion VSRRRRRRGGRRRR has since been isolated.

[13] In gene therapy, protamine sulfate's ability to condense plasmid DNA along with its approval by the U.S. Food and Drug Administration (FDA) have made it an appealing candidate to increase transduction rates by both viral[14] and nonviral (e.g. utilizing cationic liposomes)[15] mediated delivery mechanisms.

Protamine has been shown to deter increases in body weight and low-density lipoprotein in high-fat diet rats.

However, emulsification of long-chain fatty acids for digestion and absorption in the small intestine is less constant in humans than rats, which will vary the effectiveness of protamine as a drug.