N-(Amino-PEG4)-N-Biotin-PEG4-acid

 CAS No.: 2100306-84-9  Cat No.: BP-501517 4.5  

N-(Amino-PEG4)-N-Biotin-PEG4-acid is a heterobifunctional PEG-based linker featuring two PEG4 segments that connect a terminal biotin moiety to a terminal carboxylic acid, with an amino-functionalized junction suitable for conjugation chemistry. Structurally, the flexible poly(ethylene glycol) chains provide hydrophilicity and conformational mobility, helping minimize steric interference between the biotin tag and the reactive end group. In PROTAC and targeted protein degradation workflows, this linker can be used to introduce a biotin handle for affinity-based capture, detection, or controlled immobilization of PROTAC assemblies, while the carboxylic acid enables coupling to complementary amine-bearing ligands or attachment to other scaffold elements through standard amide-forming strategies. Its PEG architecture supports aqueous solubility and can improve functional presentation of bulky targeting and E3-recruiting components, making it valuable for assembling, characterizing, and optimizing targeted degradation constructs in vitro.

N-(Amino-PEG4)-N-Biotin-PEG4-acid

Structure of 2100306-84-9

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PROTAC Linker
Molecular Formula
C₃₁H₅₈N₄O₁₂S
Molecular Weight
710.88

* For research and manufacturing use only. Not for human or clinical use.

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IUPACName
3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoyl-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
InChI Key
AZKXAZTWSKMXDE-VWYPKUQYSA-N
InChI
InChI=1S/C31H58N4O12S/c32-6-10-41-14-18-45-22-24-47-20-16-43-12-8-35(7-11-42-15-19-46-23-21-44-17-13-40-9-5-29(37)38)28(36)4-2-1-3-27-30-26(25-48-27)33-31(39)34-30/h26-27,30H,1-25,32H2,(H,37,38)(H2,33,34,39)/t26-,27-,30-/m0/s1
SMILES
C1C2C(C(S1)CCCCC(=O)N(CCOCCOCCOCCOCCC(=O)O)CCOCCOCCOCCOCCN)NC(=O)N2
1. Development of N-F fluorinating agents and their fluorinations: Historical perspective
Teruo Umemoto, Yuhao Yang, Gerald B Hammond Beilstein J Org Chem. 2021 Jul 27;17:1752-1813.doi: 10.3762/bjoc.17.123.eCollection 2021.
This review deals with the historical development of all N-F fluorinating agents developed so far. The unique properties of fluorine make fluorinated organic compounds attractive in many research areas and therefore fluorinating agents are important. N-F agents have proven useful by virtue of their easy handling. This reagent class includes many types of N-F compounds: perfluoro-N-fluoropiperidine, N-fluoro-2-pyridone, N-fluoro-N-alkylarenesulfonamides, N-fluoropyridinium salts and derivatives, N-fluoroquinuclidium salts, N-fluoro-trifluoromethanesulfonimide, N-fluoro-sultams, N-fluoro-benzothiazole dioxides, N-fluoro-lactams, N-fluoro-o-benzenedisulfonimide, N-fluoro-benzenesulfonimide, 1-alkyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane salts, N-fluoropyridinium-2-sulfonate derivatives, 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane salts, N-fluorodinitroimidazole, N-fluoro-trichloro-1,3,5-triazinium salt, N-F ethano-Tröger's base derivatives, N-fluoro-methanesulfonimide, N-fluoro-N-arylarenesulfonamides, bisN-F salts such as N,N'-difluorobipyridinium salts and N,N'-difluoro-1,4-diazoniabicyclo[2.2.2]octane salts, and their many derivatives and analogs, including chiral N-F reagents such as optically active N-fluoro-sultam derivatives, N-fluoro-alkaloid derivatives, DABCO-based N-F derivatives, and N-F binaphthyldisulfonimides. The synthesis and reactions of these reagents are described chronologically and the review also discusses the relative fluorination power of each reagent and their mechanisms chronicling developments from a historical perspective.
2. Crystal structures of three N,N,N'-tris-ubstituted thio-ureas for reactivity-controlled nanocrystal synthesis
Evert Dhaene, Isabel Van Driessche, Klaartje De Buysser, Kristof Van Hecke Acta Crystallogr E Crystallogr Commun. 2022 Jan 14;78(Pt 2):184-190.doi: 10.1107/S2056989022000147.eCollection 2022 Jan 1.
The synthesis and single-crystal X-ray structures of three N,N,N'-tris-ubstituted thio-ureas are reported, namely N,N,N'-tri-benzyl-thio-urea, C22H22N2S (1), N-methyl-N,N'-di-phenyl-thio-urea, C14H14N2S (2), and N,N-di-n-butyl-N'-phenylthio-urea, C15H24N2S (3). The influence of the different substituents on the thio-ureas is clear from the delocalization of the thio-urea C-N and C=S bonds, while the crystal structures show infinite chains of N,N,N'-tri-benzyl-thio-urea (1), hydrogen-bonded pairs of N-methyl-N,N'-di-phenyl-thio-urea (2) and hexa-mer ring assemblies of N,N-di-n-butyl-N'-phenylthio-urea (3) mol-ecules. The above-mentioned compounds were synthesized via a mild, general procedure, readily accessible precursors and with a high yield, providing straightforward access to a whole library of thio-ureas.
3. Histoplasmosis in Children; HIV/AIDS Not a Major Driver
Bassey E Ekeng, Kevin Edem, Ikechukwu Amamilo, Zachary Panos, David Denning, Rita O Oladele J Fungi (Basel). 2021 Jun 30;7(7):530.doi: 10.3390/jof7070530.
The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, several cases of histoplasmosis were documented both in the pediatric and adult populations. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939-2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), Hyper immunoglobulin M and E syndromes (n = 15, 1.2%), pancytopenia (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.

This PROTAC linker, N-(Amino-PEG4)-N-Biotin-PEG4-acid, provides a biotin-functionalized, polyethylene glycol–based spacer architecture that supports flexible conjugation and efficient spatial presentation of binding motifs. Its hydrophilic PEG segments help reduce nonspecific interactions and improve solubility in typical PROTAC assembly workflows. The amino functionality enables robust coupling to target-binding ligands, while the biotin handle can be used for affinity-based handling or modular construct design. Detailed structural and reaction considerations are provided below.

Structure: The linker comprises two polyethylene glycol segments flanking a central amine, terminating in a biotin-derived moiety and a carboxylic acid. It contains ether linkages characteristic of PEG, an amide-forming amino group, and a terminal carboxyl group for activation. The overall structure is highly polar and conformationally flexible.

Reactivity: The carboxylic acid is suitable for standard PROTAC linker coupling via activation to reactive intermediates such as active esters or acid chlorides, followed by nucleophilic amide bond formation with amine-bearing ligands. Typical coupling employs coupling reagents and base in polar organic solvents, with mild conditions to preserve sensitive functional groups. The PEG-rich backbone generally tolerates common esterification and amidation chemistries while maintaining aqueous compatibility for subsequent purification and conjugation steps.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2

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Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
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