Basic Peptide Prime

What is a peptide?

Peptides (proteins) are present in every living cell and possess a variety of biochemical activities. Some peptides are synthesized in the ribosomes of a cell by translation of mRNA (messenger RNA) into hormones and signaling molecules for example. Other peptides are assembled (rather then synthesized) and become enzymes with a vast variety of functions. Peptides also make up the structure of receptors which await binding of hormones & signaling molecules.

A peptide is a molecule created by joining two or more amino acids. In general if the number of amino acids is less than fifty, these molecules are called peptides, while larger sequences are referred to as proteins.

So peptides can be thought of as tiny proteins. They are merely strings of amino acids.

Raw Constituents of Peptides (Amino Acids)

Amino acids are small molecules made up of atoms. As part of their structure they posses a grouping of a Nitrogen (N) atom bonded to two Hydrogen (H) atoms. This is called an amino group and written as (NH2). In addition their structure is also made up of a second grouping of a Carbon (C) atom bonded to two Oxygen (O) and one Hydrogen atom. This group is called a carboxyl group and is written as (COOH).

Between these two groupings are atoms and bonds unique to each amino acid. In other words all amino acids possess the two groupings (amino& carboxyl) as end-points between which are sandwiched a unique set of atoms.

Amino Acids

Inside the human body there are twenty standard amino acids used by cells in peptide biosynthesis (i.e. the cellular creation of peptides from amino acids). Our genetic code specifies how to synthesize peptides and proteins from these amino acids.

Amino acids are classified into two groups: essential amino acids and nonessential amino acids.

An essential amino acid is an indispensable amino acid which cannot be made by the body and must be supplied by food. These include isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Another amino acid – histidine is considered semi-essential because the body does not always require dietary sources of it.

Nonessential amino acids are made by the body from the essential amino acids or the routine breakdown of proteins. The nonessential amino acids are arginine, alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine.

All twenty amino acids are equally important in maintaining a healthy body. They are the raw constituents of peptides and proteins.

The standard abbreviations for amino acids come in two forms: a one letter form and a three letter form. They are:

A – Ala – Alanine C – Cys – Cysteine D – Asp – Aspartic Acid E – Glu – Glutamic Acid F – Phe – Phenylalanine G – Gly – Glycine H – His – Histidine I – Ile – Isoleucine K – Lys – Lysine L – Leu – Leucine M – Met – Methionine N – Asn – Asparagine P – Pro – Proline Q – Gln – glutamine R – Arg – Arginine S – Ser – Serine T – Thr – Threonine V – Val – Valine W – Trp – Tryptophan Y – Tyr – Tyrosine

Amino acids exist in either D (dextro) or L (levo) form. Most of the amino acids found in nature (and all within human cells) are of the L-form. As a generality all amino acids except glycine have a mirror image of the L-form. This mirror image is called the D-form. It is common when referring to the L-form (naturally occurring form) to leave off the “L” designation whereas the “D” designation is always explicitly written.

D-amino acids are found naturally in bacterial cell walls and used in some synthetic peptides to make a peptide more stable or more resistant to degradation.

Amino Acid + Amino Acid = Peptide

The amino acids are joined together by what is known as a “peptide bond”. A “peptide bond” is a linkage in which the nitrogen atom of one amino acid (from the amino group (NH2) binds to the carbon atom of another amino acid’s carboxyl group (COOH).

During this binding process a molecule of water is released. This is called a condensation reaction.

The resulting CO-NH bond is called a peptide bond, and the resulting molecule is called an amide.

On the following image note that the COOH group gives up an Oxygen Hydrogen (OH) bond and the NH2 group gives up a Hydrogen (H). This forms H2O, which is a water molecule which is not part of the newly created peptide. NOTE: in the following image the C (carbon) symbol is missing as it is assumed so I indicate it with a blue square.

This reaction creating a peptide bond between two amino acids creates a peptide. We can call this peptide (made up of two amino acids) a dipeptide.

This process can be repeated using the twenty amino acids as raw material to create longer peptide chains. Sometimes peptide chains consisting of fifty to 100 amino acids are called polypeptides. Often a peptide chain beyond 100 amino acids is called a protein.

GHRP-6 is a peptide made up of just six amino acids. It’s structure is often written as His-DTrp-Ala-Trp-DPhe-Lys-NH2

Note that the Carboxyl grouping (COOH) is assumed in the first position and is usually not written. The amino group (NH2) is wrtitten in the last position. The “meat” or the part that makes GHRP-6 distinct is the seqence in the middle of histadine bonded to the “D” form of Tryptophan bonded to Alanine bonded to Tryptophan bonded to the “D” form of Phenylalanine bonded to Lysine.

Pepdide bonds are formed by water (H2O) condensation (removing water). The converse is also true. A peptide bond can be broken down by hydrolysis (adding water).

The Amino Acid Structures of Peptides discussed in this thread

Growth Hormone Releasing peptides (GHRPs) (GH pulse initiators):

  • GHRP-6 (His-DTrp-Ala-Trp-DPhe-Lys-NH2)
  • GHRP-2 (DAla-D-2-Nal-Ala-Trp-DPhe-Lys-NH2)
  • Hexarelin (His-D-2-methyl-Trp-Ala-Trp-DPhe-Lys-NH2)
  • Ipamorelin (Aib-His-D-2-Nal-DPhe-Lys-NH2) – Ref-1 NOTES: Aib = Aminoisobutyryc acid D-2-Nal = “D” form of 2’-naphthylalanine

Growth Hormone Releasing Hormone (GHRH) (amplifies the GHRP initiated pulse):

  • Growth Hormone Releasing Hormone (GHRH) aka GRF(1-44) (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2) = half-life “less then 10 minutes”, perhaps as low as 5 minutes. – Ref-2
  • GRF(1-29) aka Sermorelin (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2) – the biologically active portion of the 44 amino acid GHRH = half-life “less then 10 minutes”, perhaps as low as 5 minutes. – Ref-3
  • Longer-lasting analogs of GRF(1-29): — replace the 2nd amino acid Alanine w/ D-Alanine only to modify GRF(1-29), D-Ala2 GRF(1-29) (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2) =half-life “closer to 10 minutes” – Ref-4

— replace the 2nd, 8th, 15th & 27th amino acids & get modified GRF(1-29) or CJC-1295 w/o the DAC (i.e. the part that will bind to albumin & make the half-life days) (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2) = Half-life at least 30 minutes or so – Ref-5

— CJC-1295 (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys-(Maleimidopropionyl)-NH2) = Half-life measured in days, – Ref-6

NOTES: Lys = linker to the Drug Affinity Complex (aka (Maleimidopropionyl))

“Since GH is released in a pulsatile manner and a higher level of GH is observed between 15 and 30 min after subcutaneous administration of GH-RH analogues, hydrolysis by trypsin-like enzymes could not affect the result of stimulation.” – Potent Trypsin-resistant hGH-RH Analogues, JAN IZDEBSKI, J. Peptide Sci. 10: 524–529 (2004)

The analog in the above quoted study resisted degradation for 30 minutes. The quote implies that if your analog can last 30 minutes it has tapped out the potential for a single pulse.

Since another pulse won’t be generated for about 2.5 – 3 hours analogs that last more than 30 minutes up to 3 hours are not any more beneficial.

You would need an analog that kept growth hormone releasing hormone around beyond 3 hours to have it trigger a second pulse.

Otherwise dosing the 30 minute analog every 3 hours will maximize GH output OR you could just use an analog such as CJC-1295 which lasts for many days and will trigger several GH pulses a day for several days on a single dose.

References:

Ref-1 – “lack of effect on ACTH and cortisol plasma levels” – Ipamorelin, the first selective growth hormone secretagogue , K Raun, European Journal of Endocrinology, 1996 Vol 139, Issue 5, 552-561

Ref-2 – Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus, Frohman LA, J Clin Invest. 1986 78:906–913 andIncorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

Ref-3 – Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus, Frohman LA, J Clin Invest. 1986 78:906–913 andIncorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

Ref-4 – Incorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

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