Name: Fmoc-Phe-Lys(Trt)-PAB-PNP
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

(9H-Fluoren-9-yl)methyl ((S)-1-(((S)-1-amino-1-oxo-6-(tritylamino)hexan-2-yl)(4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate;

IUPAC Name

Canonical SMILES

C1=CC=C(C=C1)CC(C(=O)N(C2=CC=C(C=C2)COC(=O)OC3=CC=C(C=C3)[N+](=O)[O-])C(CCCCNC(C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)C(=O)N)NC(=O)OCC7C8=CC=CC=C8C9=CC=CC=C79

InChI

InChI=1S/C63H57N5O9/c64-59(69)58(31-17-18-40-65-63(46-21-7-2-8-22-46,47-23-9-3-10-24-47)48-25-11-4-12-26-48)67(49-34-32-45(33-35-49)42-76-62(72)77-51-38-36-50(37-39-51)68(73)74)60(70)57(41-44-19-5-1-6-20-44)66-61(71)75-43-56-54-29-15-13-27-52(54)53-28-14-16-30-55(53)56/h1-16,19-30,32-39,56-58,65H,17-18,31,40-43H2,(H2,64,69)(H,66,71)/t57-,58-/m0/s1

InChIKey

LOGURWMJSNXIEZ-YQOHNZFASA-N

Appearance

Soild powder

Shipping

-20°C (International: -20°C)

Fmoc-Phe-Lys(Trt)-PAB-PNP is a multifunctional compound used in peptide synthesis, bioconjugation, and drug delivery systems. The Fmoc (9-fluorenylmethyloxycarbonyl) group protects the N-terminal amino group, enabling precise sequential peptide assembly through solid-phase peptide synthesis (SPPS). This protection facilitates the incorporation of the compound into complex peptide chains with high specificity and efficiency, making it a valuable building block in advanced biochemical applications.

The Fmoc-Phe-Lys(Trt) core combines phenylalanine (Phe) and lysine (Lys) residues, with the Trt (trityl) group protecting the side chain amino group of lysine. This dual protection scheme ensures stability during synthesis and allows for selective functionalization of the lysine residue. This functionality is particularly useful in designing peptide-drug conjugates (PDCs) and targeted delivery systems, where the lysine side chain serves as a critical attachment point for therapeutic agents, imaging probes, or other bioactive molecules.

The PAB (para-aminobenzyl) moiety is a key feature of Fmoc-Phe-Lys(Trt)-PAB-PNP, acting as a self-immolative linker. This property enables controlled release of payloads upon cleavage of the peptide or linker sequence. In drug delivery, the PAB linker ensures efficient release of attached drugs or toxins in response to specific triggers, such as enzymatic activity or changes in pH. This mechanism is essential for the design of antibody-drug conjugates (ADCs) and other targeted therapies, enabling precise release of cytotoxic agents at diseased sites while minimizing systemic toxicity.

The PNP (p-nitrophenyl) group further enhances the versatility of Fmoc-Phe-Lys(Trt)-PAB-PNP by serving as a leaving group in nucleophilic substitution reactions. This feature allows for the conjugation of a wide range of functional groups, making the compound a valuable tool in bioconjugation and surface modification. Applications include the attachment of peptides to nanoparticles, polymers, or other biomaterials for use in drug delivery, diagnostics, and biomaterial engineering.

Fmoc-Phe-Lys(Trt)-PAB-PNP is also employed in the development of protease-sensitive linkers. By incorporating enzyme-cleavable sequences, the compound enables precise drug release in response to proteolytic activity in disease-specific environments, such as tumors. This property is crucial for the development of advanced therapeutic strategies, including prodrugs and stimuli-responsive drug delivery systems.

1. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology

Michael Zitzmann, Dirk Vanderschueren, Ilpo Huhtaniemi, Dimitrios G Goulis, Giovanni Corona, Gianni Forti, Jorma Toppari, Frederick C Wu Andrology . 2020 Sep;8(5):970-987. doi: 10.1111/andr.12770.

Background:Evidence regarding functional hypogonadism, previously referred to as 'late-onset' hypogonadism, has increased substantially during the last 10 year.Objective:To update the European Academy of Andrology (EAA) guidelines on functional hypogonadism.Methods:Expert group of academicians appointed by the EAA generated a series of consensus recommendations according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.Results:The diagnosis of functional hypogonadism should be based on both the presence of clinical symptoms supported by repeatedly low morning fasting serum total testosterone (T) measured with a well-validated assay, after exclusion of organic causes of hypogonadism. Lifestyle changes and weight reduction should be the first approach in all overweight and obese men. Whenever possible, withdrawal/modification of drugs potentially interfering with T production should be advised. Testosterone replacement therapy (TRT) is contraindicated in men with untreated prostate or breast cancer, as well as severe heart failure. Severe low urinary tract symptoms and haematocrit >48%-50% represent relative contraindications for TRT. Prostate-specific antigen and digital rectal examination of the prostate should be undertaken in men >40 years of age before initiating TRT to exclude occult prostate cancer. Transdermal T should be preferred for initiation of TRT, whereas gonadotrophin therapy is only recommended when fertility is desired in men with secondary hypogonadism. TRT is able to improve sexual function in hypogonadal men. Other potential positive outcomes of TRT remain uncertain and controversial.Conclusion:TRT can reliably improve global sexual function in men with hypogonadism in the short term. Long-term clinical benefits, and safety of TRT in functional hypogonadism, remain to be fully documented. Clinicians should therefore explicitly discuss the uncertainties and benefits of TRT and engage them in shared management decision-making.

2. Testosterone and the Prostate

Wayne J G Hellstrom, Ronny B W Tan, Jonathan L Silberstein Sex Med Rev . 2014 Oct;2(3-4):112-120. doi: 10.1002/smrj.29.

Introduction:Late-onset hypogonadism, lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), and prostate cancer commonly coexist in the aging male. Due to a better understanding of the physiology and impact of testosterone on benign and malignant diseases of the prostate, the view toward testosterone replacement therapy (TRT) in these individuals has changed dramatically over time.Aim:This communication evaluates the effects of testosterone on benign prostatic growth and prostate cancer and reviews the evidence for TRT for men with BPE and prostate cancer.Methods:A literature review was performed with regards to TRT in men with prostate cancer as well as the effect of testosterone on the growth of benign prostate tissue and prostate cancer carcinogenesis.Main outcome measure:To evaluate the evidence for an effect of testosterone on the growth of benign prostate tissue and the development of prostate cancer and TRT in men with prostate cancer.Results:TRT does not exacerbate LUTS. Current evidence is lacking but suggests that TRT may not increase the risk of subsequent diagnosis of prostate cancer, and is unlikely to impact recurrence or progression for men with treated prostate cancer, but longer follow-up is needed.Conclusions:There is no evidence to suggest that TRT is contraindicated in men with BPE or effectively treated prostate cancer. Tan RBW, Silberstein JL, and Hellstrom WJG. Testosterone and the prostate. Sex Med Rev 2014;2:112-120.

3. Testosterone replacement therapy in the era of telemedicine

Richard J Fantus, Joshua A Halpern, Justin M Dubin Int J Impot Res . 2022 Nov;34(7):663-668. doi: 10.1038/s41443-021-00498-5.

The events of the 2019 SARS-CoV2 virus pandemic have all but ensured that telemedicine will remain an important aspect of patient care delivery. As health technologies evolve, so must physician practices. Currently, there is limited data on the management of testosterone replacement therapy (TRT) in the era of telemedicine. This review aims to explore the potential benefits and pitfalls of TRT management via telemedicine. We also propose a theoretical framework for TRT management via telemedicine. Telemedicine provides patients and physicians with a new mechanism for American Urological Association guideline-concordant TRT management that can increase patient access to care and provide a safe space for men who may otherwise not have been comfortable with in-person evaluation. However, there are significant limitations to the use of telemedicine for the management of TRT, including the inability to perform a physical exam, inability to administer specific medications, technological barriers, data security, and medical-legal considerations, and both patients and providers should engage in shared decision making before pursuing this approach. Understanding and acknowledging the potential pitfalls of telemedicine for TRT management will enable both patients and providers to achieve optimal outcomes and satisfaction.