Short Chain Proteins

Short Chain Proteins / Oligopeptides

Short chain proteins, also known oligopeptides, are molecules comprised of a chain of two to twenty amino acids. They stand in contrast to polypeptides or long chain proteins, which are comprised of more than twenty – sometimes even hundreds or thousands of – amino acids.¹

he main difference between short chain proteins and globular proteins or polypeptides is their size and length. On the one hand, short chain proteins are made of two to fifty amino acids joined through peptide bonds. These compounds are much smaller than long chain polypeptides. However, they have weaker intramolecular bonds which allow them to easily change their configuration.

On the other hand, a globular protein molecule is comprised of one or more polypeptide chains, each containing at least thirty amino acids, sometimes much more. Globular proteins are also able to change configuration but not to the same extent as short chain proteins, which often act as regulatory agents for protein function.²

Proteins

The Merriam-Webster definition of a protein is:

“Any of various naturally occurring extremely complex substances that consist of amino-acid residues joined by peptide bonds, contain the elements carbon, hydrogen, nitrogen, oxygen, usually sulfur, and occasionally other elements (as phosphorus or iron), and include many essential biological compounds (as enzymes, hormones, or antibodies)”³

The structure of a protein molecule determines its function. This is due to the biochemical importance of protein folding and the electrochemical attributes of amino-acids. As a result, proteins have vitally important roles to play in all living organisms. Some of the key protein functions include:

1. Antibody Proteins: Antibodies are vital components of the immune system and bind to foreign particles like viruses and bacteria to trigger an immune response
2. Enzyme Proteins: Enzymes act as catalysts for the biochemical reactions occurring in living organisms
3. Messenger Proteins: Messenger proteins like hormones help to transmit signals from various parts of the body and coordinate biological functions
4. Structural Components: Larger proteins provide structure to cells by acting as a ‘scaffolding’, as well as allowing movement of the body
5. Transport/Storage Proteins: Transport proteins are often found in cell membranes and help carry smaller molecules across an unfavorable osmotic gradient⁴

Short Chain Protein Functions

Research into oligopeptide function has indicated the existence of over 6000 short chain protein peptides that occur in nature. The full catalog of oligopeptides with known biological, chemical, and physical properties has been compiled on the EROP-Moscow (Endogenous Regulatory OligoPeptides) website.

Research has pointed to the key function of short chain peptides (under 50 amino acids in length) as being biochemical regulators. The first oligopeptide, carnosine (β-ala-his), was discovered by Gulevitch and Amiradzhibi in 1900, and its chemical structure was elucidated in 1918.⁵

The key function of carnosine, and several other bipeptides, is to act as a cytocylic buffering agent with strong antioxidant properties. Other roles may include acting as neurotransmitters and the modulation of enzyme activity.⁶

Like the globular proteins, a characteristic of the short chain proteins is the fact that their structure determines their function. Specifically, small amino acid sequences have weak enough intramolecular bonds that they are able to change configuration to fit into receptor molecules and larger proteins.⁷

As a result, one of the primary functions of short chain proteins is to regulate the activity of larger proteins – specifically enzyme and transporter protein functionality. Another key function of oligopeptides is proton-dependent transport and signaling.⁸

Oligopeptide Applications

As a result of the regulatory function of the small chain proteins, and their ability to alter the function of larger proteins, they have a varied and exciting range of potential applications.

Short amino acid sequence-based compounds already have a broad range of clinical applications, including in the treatment of AIDS, cancer, and hypertension. Many of these chemical agents specifically target oligopeptide transporters (proton-dependent transporters) for the application of their effects.⁹

n 2015, there were around 140 amino-acid based agents with a potential therapeutic value being investigated in clinical trials. This number is predicted to grow to around 500 by 2018. The market value of short chain protein agents is predicted to grow from US$14.1 billion in 2011 to an estimated US$25.4 billion in 2018.¹⁰

The ability of short chain proteins and peptide-based agents to act as neurotransmitters, hormones, growth factors, transporters, and antibiotics, gives them a real value in pharmaceutical research. The majority of peptide-based agents are used in the treatment of metabolic diseases and in oncology research. A recent example of peptide-based agents is the glucagon-like peptide-1 (GLP-1) agonists, used in the treatment of type 2 diabetes.¹¹

Other interesting examples of short chain proteins include:

1. Amanitin, a toxic chemical found in several mushroom species which inhibits the function of RNA Polymerase 2 and is used in RNA transcription research
2. Glutathione – a tripeptide with important cellular functions, including the binding to toxins and drugs, and acting as an enzyme cofactor
3. Netropsin – A cytotoxin derived from bacteria and used in genetics research
4. Teprotide – A laboratory-made amino acid sequence that is identical to the Jararaca (pit viper) snake poison, used for antihypertensive applications¹²

Short Chain Proteins SWOT Analysis

A brief SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis for Short Chain proteins shows some interesting results of their application in industry.

Strengths include that short chain proteins have high efficacy and safety, as well as strong potency and selectivity. They also have a predictable metabolism and a shorter time to market than other chemical agents.

However, their weaknesses include the fact that they are chemically unstable (prone to hydrolysis and oxidation), have a short half-life, are often not available for oral use, and have a low membrane permeability.

Numerous opportunities exist in the field of short chain protein research, including the discovery of new agents, the creation of new databases, research into alternative administration routes, and the development of multifunctional short chain proteins.

Threats to the further development of short chain proteins as therapeutic agents include the possibility of immunogenicity in response to the agent, as well as business-related threats like competition and patenting issues.¹³

NewMind Short Chain Proteins

Noopept (GVS-111) is currently the single short chain protein available on NewMind. It is a Nootropic compound derived from the Racetam family. Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) contains an amino group joined with a peptide bond to a pyrrolidine ring and can therefore be considered as a short chain protein.¹⁴

Noopept was traditionally marketed as a Nootropic with a potency 1000 times greater than that of Piracetam. It was originally developed in 1996 as a dipeptide derivative of Piracetam. It is water-soluble and is known to increase endogenous Cycloprolylglycine concentrations.¹⁵

Furthermore, research has indicated the potential application for Noopept in neuroscience research. Noopept increases spindle-like acivity as well as alpha brain-wave activity in animal models.¹⁶

Single doses of Noopept increase both NGF and BDNF mRNA concentrations in animal models. The increased neurotrophin concentrations of interest to researchers in the fields of cognition and neuroscience.¹⁷

Toxicity and Warnings

All chemicals on NewMind are specifically not for human consumption. They are not to be used on human volunteers in research, nor are they for veterinarian applications. Short chain proteins are considered to have high safety and tolerance profiles when compared to other synthetic agents.

Many of the substances available on NewMind do not yet have a large body of research to investigate their toxicity. Most compounds have an established LD50 or LD0, but not all. For more information about toxicity/warnings, please read through the write-up for the specific NewMind product in interest.

Furthermore, we ask that researchers conduct their own research prior to purchasing NewMind products. PubMed is a good source of data on published studies and clinical trials pertaining to the products available on this website.

¹ B Lewandowski, H Wennemers “Asymmetric catalysis with short-chain peptides”, Current Opinion in Chemical Biology, Volume 22, October 2014, Pages 40–46, DOI: 10.1016/j.cbpa.2014.09.011

² “The Structure of Proteins”, R Bowen, Colombo State University notes online, 2002, accessed April 12, 2017

³ “Protein”, Definition of ‘Protein’, Merriam-Webster dictionary, available online, accessed April 12, 2017

⁴ “What are proteins and what do they do?”, Genetics Home Reference, US National Library of Medicine, available online, accessed April 12, 2017

⁵ L Baumann, T Ingvaldsen, “CONCERNING HISTIDINE AND CARNOSINE. THE SYNTHESIS”, J. Biol. Chem. 1918, 35:263-276

⁶ PJ Quinn et al., “Carnosine: its properties, functions and potential therapeutic applications”, Mol Aspects Med. 1992;13(5):379-444.

⁷ A Spaar et al., “Conformation of Peptides in Lipid Membranes Studied by X-Ray Grazing Incidence Scattering”, Biophys J. 2004 Jul; 87(1): 396–407, doi: 10.1529/biophysj.104.040667

⁸ AA. Zamyatnin et al., “The EROP-Moscow oligopeptide database”, Nucleic Acids Res. 2006 Jan 1; 34(Database issue): D261–D266, Published online 2005 Dec 28. doi: 10.1093/nar/gkj008

⁹ R. Krishna, L. Yu (Eds.), “Biopharmaceutics Applications in Drug Development”, pp 195-196, Springer, 2008, XXII, 396 p.

¹⁰ Transparency Market Research: “Peptide Therapeutics Market: Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2012–2018”, Press Release Published Date: 2015-04-27, accessed April 12, 2017

¹¹ C McDougall et al., “Drugs for Diabetes”, Br J Cardiol. 2011;18(4):167-169.

¹² P Argos, “An investigation of oligopeptides linking domains in protein tertiary structures and possible candidates for general gene fusion”, J Mol Biol. 1990 Feb 20;211(4):943-58.

¹³ K Fosgerau, T Hoffmann, “Peptide therapeutics: current status and future directions”, Drug Discovery Today, Volume 20, Issue 1, January 2015, Pages 122-128, DOI: 10.1016/j.drudis.2014.10.003

¹⁴ “Noopept, CID 180496”, PubChem, Open Chemistry Database, US National Library of Medicine, accessed April 12, 2017

¹⁵ “Noopept”, Examine.com, accessed April 12, 2017

¹⁶ Ostrovskaya RU et al., “Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation”, J Biomed Sci. 2014 Aug 6;21:74. doi: 10.1186/s12929-014-0074-2.

¹⁷ Ostrovskaya RU et al., “Noopept stimulates the expression of NGF and BDNF in rat hippocampus”, Bull Exp Biol Med. 2008 Sep;146(3):334-7.