N-Acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide
[CAS# 448944-47-6]

Identification

• Classification: Biochemical >> Peptide
• Name: N-Acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide
• Synonyms: (2S)-2-acetamido-N-[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]hexanamide
• Protein Sequence: XAHFRW
• Molecular Formula: C₄₃H₅₉N₁₃O₇
• Molecular Weight: 870.01
• CAS Registry Number: 448944-47-6
• SMILES: CCCC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)N)NC(=O)C

Properties

• Solubility: Practically insoluble (0.076 g/L) (25 ºC), Calc.^*
• Density: 1.39±0.1 g/cm³ (20 ºC 760 Torr), Calc.^*
• Index of refraction: 1.667 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

N-Acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide is a synthetic hexapeptide derivative characterized by a defined sequence of amino acid residues with specific stereochemistry and terminal modifications. The molecule contains an N-acetylated amino terminus and an amidated carboxyl terminus, structural features that are commonly introduced to enhance stability against enzymatic degradation and to modulate biological activity. Peptides of this type emerged from advances in peptide chemistry and endocrinology during the second half of the twentieth century.

The discovery of peptides with precisely controlled sequences became feasible following the development of reliable peptide synthesis methods. Early peptide research relied on laborious solution-phase techniques, but the introduction of solid-phase peptide synthesis enabled chemists to assemble complex sequences with high fidelity. Within this context, N-acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide was prepared as part of systematic investigations into biologically active peptide analogs. The deliberate incorporation of a D-configured phenylalanine residue reflects a common strategy used to probe structure–activity relationships and to improve resistance to proteolytic enzymes.

The peptide sequence itself is closely related to motifs found in neuropeptides and regulatory peptides that act on specific receptors in the nervous and endocrine systems. During the period when such compounds were first synthesized, researchers were actively exploring how subtle changes in amino acid composition, stereochemistry, and terminal groups could influence receptor binding and biological response. N-acetylation and C-terminal amidation were recognized as particularly important modifications, as they often mimic the natural post-translational processing of endogenous peptides.

Chemically, the peptide exemplifies key principles of peptide design. The presence of basic residues such as arginine contributes to overall charge and receptor interaction, while aromatic residues such as phenylalanine and tryptophan play a role in hydrophobic interactions and binding specificity. Histidine can participate in hydrogen bonding and pH-dependent interactions, adding another layer of functional complexity. Norleucine, a non-proteinogenic amino acid, is frequently used as a substitute for methionine to avoid oxidation while maintaining similar steric properties. These considerations highlight the rational design approach underlying the synthesis of this compound.

The primary applications of N-acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide have been in biochemical and pharmacological research. Such peptides have been used as experimental tools to study receptor activation, signal transduction pathways, and hormone-like activities in vitro and in vivo. By comparing the biological effects of this peptide with those of related sequences, researchers have been able to identify critical residues required for activity and to map regions responsible for receptor selectivity.

In addition to receptor studies, peptides of this class have been employed as reference compounds in analytical chemistry. Their well-defined composition makes them suitable for validating chromatographic and spectrometric methods used in peptide analysis. The compound’s stability, conferred by its terminal modifications and inclusion of a D-amino acid, further supports its use in controlled experimental settings.

Although N-acetyl-L-norleucyl-L-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophanamide is not a therapeutic agent in routine clinical use, its role in research has been significant. It represents a generation of synthetic peptides that bridged fundamental chemistry and biology, enabling precise manipulation of molecular structure to explore biological function. Through its use, scientists have gained deeper insight into peptide–receptor interactions and the principles governing peptide stability and activity.

Overall, this compound illustrates the impact of synthetic peptide chemistry on modern biomedical research. Its discovery arose from methodological advances in peptide synthesis, and its applications have contributed to a more detailed understanding of how specific amino acid sequences and modifications translate into biological effects.

References

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