Tesamorelin Molecular Weight, Sequence & CAS Reference

Chemical Overview and Molecular Identity

Tesamorelin is a synthetic peptide analog of human growth hormone-releasing hormone (GHRH). Structurally, it consists of the full 44-amino acid sequence of human GHRH with a specific lipophilic modification attached to the N-terminal residue: a trans-3-hexenoyl group. This N-terminal hexenoyl modification was specifically engineered to enhance resistance to enzymatic degradation by dipeptidyl peptidase-4 (DPP-4), thereby extending its biological half-life compared to native GHRH(1-44) amide in experimental systems.

In biochemical literature and physical repositories, tesamorelin is classified as a synthetic GHRH receptor agonist. Designed for laboratory research use only, high-grade research preparations such as tesamorelin 10mg are utilized in preclinical research to investigate the mechanics of the somatotropic axis, growth hormone (GH) pulsatility, and downstream insulin-like growth factor 1 (IGF-1) signalling pathways. Understanding its exact physical parameters—including net weight, salt counterions, and residue sequence—is essential for accurate molar calculations in quantitative assays.

Primary Amino Acid Sequence and Structural Modification

The primary structure of tesamorelin comprises 44 amino acid residues in a linear sequence, terminated with a C-terminal carboxamide group (-NH2) and an N-terminal trans-3-hexenoyl moiety. The hydrophobic hexenoyl tail provides steric hindrance against cleavage at the Ala2-Asp3 peptide bond by cleavage enzymes.

The complete primary sequence (using single-letter and three-letter amino acid notation) is as follows:

Sequence (Three-Letter Code): (Trans-3-hexenoyl)-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

Sequence (One-Letter Code): (Trans-3-hexenoyl)-YADAIFTNSYRKVLGLSARLKLLQDIMSRQQGESNQERGARARL-NH2

The terminal C-terminal leucine residue is amidated, which mimics the endogenous human GHRH molecule and preserves binding affinity for the GHRH receptor expressed on anterior pituitary somatotrophs.

Molecular Weight, Empirical Formula, and Mass Spectrometry

Calculating the molecular weight of a modified peptide requires accounting for both the peptide backbone, C-terminal amidation, N-terminal acyl modification, and any bound salt adducts. For free base tesamorelin, the theoretical physical constants are established as follows:

Empirical Formula: C221H366N72O67S Monoisotopic Mass: 5132.77 Da Average Molecular Weight: 5135.89 g/mol (or Da)

When analyzing tesamorelin via Electrospray Ionization Mass Spectrometry (ESI-MS) or Matrix-Assisted Laser Desorption/Ionization (MALDI-TOF), researchers typically observe multivalent protonated charge states (e.g., [M+4H]4+, [M+5H]5+, [M+6H]6+) due to the abundance of basic residues (Arg and Lys) within the sequence. Mass spectrometry profiles must match the theoretical molecular weight of 5135.89 Da (base) to confirm identity and exclude truncation sequences or incomplete acyl couplings during solid-phase peptide synthesis (SPPS).

CAS Registry Numbers and Chemical Identification

Chemical Abstract Service (CAS) numbers provide unambiguous identification for chemical substances across international chemical databases, research publications, and material safety data sheets (MSDS). Because peptides can exist as free bases or specific salt forms, distinct CAS identifiers are assigned:

Tesamorelin (Free Base CAS): 218949-48-5 Tesamorelin Acetate (Salt Form CAS): 901758-09-6 IUPAC Name: (trans-hex-3-enoyl)-[Tyr1,Ala2,Asp3,Ala4,Ile5,Phe6,Thr7,Asn8,Ser9,Tyr10,Arg11,Lys12,Val13,Leu14,Gly15,Gln16,Leu17,Ser18,Ala19,Arg20,Lys21,Leu22,Leu23,Gln24,Asp25,Ile26,Met27,Ser28,Arg29,Gln30,Gln31,Gly32,Glu33,Ser34,Asn35,Gln36,Glu37,Arg38,Gly39,Ala40,Arg41,Ala42,Arg43,Leu44]-NH2

In commercial cataloging across the broader landscape of all peptides, verifying the CAS reference ensures that investigator teams receive the precise chemical moiety specified in their experimental protocol.

Salt Forms: Acetate vs. Trifluoroacetate (TFA) Counterions

During solid-phase synthesis, peptides are cleaved from resins using trifluoroacetic acid (TFA), leaving basic amino acid side chains (such as Arginine and Lysine) protonated with TFA counterions. In tesamorelin, which contains 7 basic residues (5 Arginine, 2 Lysine) plus the N-terminus, multiple counterions bind to each peptide molecule.

Depending on post-cleavage purification and lyophilization steps, research peptides are supplied as either TFA salts or converted to Acetate salts:

1. Trifluoroacetate (TFA) Salt: Common in raw synthetic isolates. While fine for standard analytical chromatography, residual TFA can exhibit cell toxicity in sensitive in vitro cell culture assays. 2. Acetate Salt: Preferred for biological in vitro assays and animal models due to lower cellular toxicity. Through ion-exchange chromatography, TFA counterions are replaced with acetate (CH3COO-) ions.

Because counterions contribute significant mass to the lyophilized powder, knowing the precise salt form is crucial when calculating molar concentrations for buffer preparations.

Net Peptide Content (NPC) vs. Purity

A common point of confusion in laboratory research is the distinction between chemical purity (measured by High-Performance Liquid Chromatography, HPLC) and Net Peptide Content (NPC, determined by Nitrogen Analysis or Amino Acid Analysis).

Chemical Purity (HPLC %): Refers to the percentage of total peptide material that consists of the target sequence without truncated fragments or oxidation products. PX1 Research mandates >98% HPLC purity for research compounds.

Net Peptide Content (NPC %): Refers to the actual percentage of peptide mass relative to total weight, which includes residual counterions (acetate/TFA) and bound water (hygroscopic moisture). For example, a 10 mg vial of tesamorelin with an 80% NPC contains 8.0 mg of actual active peptide peptide base and 2.0 mg of counterions and moisture.

To verify these parameters for specific research lots, investigators should always consult the lot-specific certificate of analysis (COA) prior to performing quantitative gravimetric dispensing.

Pharmacodynamics: GHRH Receptor Binding and Signaling Pathways

In preclinical settings, tesamorelin functions as a selective ligand for the Growth Hormone-Releasing Hormone Receptor (GHRHR), a G-protein coupled receptor (GPCR) expressed primarily on somatotroph cells of the anterior pituitary gland.

Upon binding to the extracellular domain of GHRHR, tesamorelin activates the Gas protein subunit, stimulating adenylate cyclase and increasing intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP triggers protein kinase A (PKA) signaling, inducing extracellular calcium influx and stimulating transcription factors such as CREB. This cascade leads to the synthesis and pulsatile release of endogenous growth hormone (GH).

Preclinical in vitro assays demonstrate that the trans-3-hexenoyl group does not impair GHRHR activation kinetics or receptor affinity. Instead, it slows clearance by plasma peptidases, resulting in prolonged downstream signalling compared to native GHRH.

Preclinical Research Applications: GH/IGF-1 Axis and Metabolic Regulation

Academic and industrial investigators utilize tesamorelin in laboratory models to investigate several physiological processes governed by the somatotropic axis:

1. Growth Hormone Pulsatility: Animal models demonstrate that pulsatile stimulation of GHRH receptors maintains natural GH feedback loops without causing early receptor downregulation or desensitization. 2. IGF-1 Induction: Circulating GH stimulates hepatic production of insulin-like growth factor 1 (IGF-1). Preclinical research measures IGF-1 induction to assess downstream anabolic and metabolic pathways. 3. Metabolic Regulation and Lipid Oxidation: Rodent models of visceral adiposity suggest that GHRH receptor activation promotes lipolysis and alters hepatic gene expression related to lipid oxidation and triglyceride synthesis. 4. Tissue Repair and Neuroprotection: In vitro and animal models evaluate the somatotropic axis in wound healing dynamics, peripheral nerve regeneration, and cellular protein synthesis.

Researchers exploring these pathways can review broader mechanisms in the PX1 peptide research hub.

Comparative Analysis: Tesamorelin vs. CJC-1295 vs. Sermorelin

When designing protocols to investigate GHRH receptor stimulation, researchers often compare tesamorelin against other synthetic secretagogues in its class:

1. Tesamorelin: A modified 44-amino acid peptide featuring an N-terminal trans-3-hexenoyl tail. Known for high selectivity and resistance to DPP-4 cleavage, making it a benchmark for visceral metabolic studies. 2. CJC-1295 (without DAC): A 29-amino acid fragment corresponding to GHRH(1-29) with four substituted amino acids (D-Ala2, Gln8, Ala15, Leu27) that confer stability. For further molecular sequence data on modified 1-29 analogs, review CJC-1295 No DAC specifications. 3. Sermorelin: The shortened 29-amino acid functional core (GHRH 1-29 amide) without N-terminal acylation. Sermorelin exhibits a rapid clearance rate and short biological half-life in vitro. Detailed structural parameters can be found on the sermorelin sequence guide.

Selecting between these compounds depends on the targeted duration of receptor occupancy and the specific metabolic endpoints under evaluation.

Laboratory Reconstitution, Buffer Compatibility, and Stability

Lyophilized tesamorelin must be reconstituted under sterile laboratory conditions using appropriate solvent systems prior to in vitro or preclinical administration. Standard laboratory solvents include Sterile Bacteriostatic Water (0.9% Benzyl Alcohol) or Sterile Normal Saline (0.9% NaCl).

Because tesamorelin is a large 44-amino acid peptide with hydrophobic regions, gentle agitation (swirling) is recommended during dissolution; aggressive vortexing should be avoided to prevent mechanical shear stress and peptide aggregation.

To calculate precise liquid volumes, final concentrations (mcg/mL), and syringe unit conversions for laboratory experiments, investigators can use the PX1 reconstitution calculator. Reconstituted solutions should be aliquoted and stored at -20°C to -80°C for long-term stability, or at 2°C to 8°C for short-term benchtop use.

Quality Assurance: HPLC, MS, and Endotoxin Standards

Reproducibility in preclinical research depends entirely on the physical purity and analytical integrity of the starting material. PX1 Research adheres to stringent quality control guidelines to ensure all research peptides meet strict ISO 17025 and GMP-compliant analytical benchmarks.

Every production lot of tesamorelin undergoes rigorous testing including reverse-phase HPLC (RP-HPLC) to confirm >98% chemical purity, ESI-MS mass spectrometry to confirm exact molecular weight (5135.89 Da base), and Chromogenic LAL testing to verify endotoxin levels remain below 0.01 EU/mg.

Institutional laboratories and bulk purchasers requiring multi-gram synthesis or custom analytical documentation can establish institutional supply channels via PX1 wholesale services. All compounds are synthesized in USA facilities and shipped directly from California and Arizona distribution hubs.