A perylenedicarboxamide linker for DNA hairpins

The synthesis and properties of a perylenediamide diol linker and several DNA hairpins possessing this linker are described. The diol linker absorbs and fluoresces strongly in the visible. Hairpins having poly(dA)-poly(dT) stems have fluorescence quantum yields and decay times similar to those of the linker, indicating that hole injection does not occur from the singlet excited linker into the base pair domain. Fluorescence quenching by dG or dZ bases is observed when these bases are located near the linker. The strong distance dependence of fluorescence quenching is consistent with a superexchange mechanism for electron transfer. Failure to observe formation of the linker anion radical by means of femtosecond time resolved absorption spectroscopy is attributed to fast charge recombination. The properties and behavior of the perylene linker and its hairpins are compared to those of other arenedicarboxamide linkers.     

A novel heterobifunctional linker for facile access to bioconjugates

A convenient synthesis of a novel heterobifunctional linker molecule is described. The linker contains a thiol-reactive nitropyridyl disulfide group (Npys) and an aldehyde-reactive aminooxy group with a propensity to form disulfide and oxime linkages. The utility of the linker molecule to cross-link different biomolecules has been demonstrated by employing it in the efficient preparation of a peptide-oligonucleotide conjugate. The linker reported herein could be a useful tool for cross-coupling of different but appropriately functionalised biomolecules.     

A nonacid degradable linker for solid-phase synthesis

Synthesis and applications of two new nonacid degradable linkers as an alternative to the Wang linker for solid-phase synthesis are described. Resin from linker 2 looks superior to linker 1 in terms of yields for both anchoring of the first building block and cleavage and in terms of higher purity of the final product. Use of linker 2 avoids side reactions associated with the use of Wang resin due to an undesired cleavage during final acid treatment.     

Dual linker with a reference cleavage site for information rich analysis of polymer-supported transformations

Two dual linker systems with specific reference cleavage sites were designed and synthesized to accelerate and simplify development and optimization of reaction conditions for solid-phase synthesis. The dual linker allows simple evaluation of cleavage rate of polymer-supported compounds from the linker and, at the same time, ensures that all resin-bound components are cleaved from the solid support. The dual linker 4 was assembled from two Wang linkers connected by a three carbon spacer. The linker 9 was synthesized using the PAL and HMPB linkers.     

3-(4-Hydroxymethylphenylsulfanyl)propanoic acid (HMPPA) as a new safety catch linker in solid phase peptide synthesis

A new safety catch linker, 3-(4-hydroxymethylphenylsulfanyl)propanoic acid (HMPPA), is described for use in solid phase peptide synthesis. The linker is readily synthesized from commercially available chemicals in a more cost efficient way compared to similar reported linkers. The HMPPA linker is easily attached to an amino derivatized solid support followed by on-resin oxidation of the thioether to sulfoxide, thereby making the linker very stable towards strong acid treatment. Final resin cleavage is performed by reductive acidolysis.     

Functionality proportion and corresponding stability study of multivariate metal-organic frameworks

Zn-based multivariate metal-organic frameworks (MTV-MOFs) with different functionality proportions and with different thermal and chemical stabilities can be obtained by employing the appropriate synthesis method.     

Nicking endonuclease and target recycles signal amplification assisted quantum dots for fluorescence detection of DNA

An ultrasensitive fluorescence detection method for DNA based on nicking endonuclease (NEase) and target recycles assisted with CdTe quantum dots (QDs) is reported. In the detection system, when the target DNA is present, it hybridizes with a linker strand to from a duplex, in which the NEase recognizes specific nucleotide sequences and cleaves the linker strand. After nicking, the fragments of the linker strand spontaneously dissociate from the target DNA and another linker strand hybridizes to the target to trigger another strand-scission cycle. On the other hand, when the target was absent, no duplex is formed and no fragment of linker strand is produced. Then CdTe QDs and magnetic beads (MBs), which were all modified with DNA sequences complementary to that of the linker strands are added to the solution to detect the presence of a target DNA. The signal was generated through the difference in F?rster resonance energy transfer (FRET) between the MB and CdTe QDs. This method indicates that one target DNA leads to cleavage of hundreds of linker DNA, increasing detection sensitivity by nearly three orders of magnitude. This method should be applicable whenever there is a requirement to detect a specific DNA sequence and can also be used for multicomponent detection.     

Practical synthesis of a dithiane-protected 3',5'-dialkoxybenzoin photolabile safety-catch linker for solid-phase organic synthesis.

The solution-phase preparation of the 3',5'-dialkoxybenzoin photolabile safety-catch linker 16 is described. Pivotal to this convenient synthesis is the selection of appropriate orthogonal protecting groups for the alkoxy functionalities present. The new linker can be readily loaded onto any standard amine-terminating resin under peptide-coupling conditions, without the need to protect the secondary alcohol functionality, and subsequently loaded with substrate. Alternatively, the loading efficiency of sterically hindered substrates can be enhanced by preloading the semiprotected linker variant 10 in solution prior to immobilization onto the resin. This second generation of benzoin photolabile safety-catch linkers provides greater control of both linker loading and resin attachment and should prove to be a more versatile and convenient form of the linker.     

A novel linker for solid-phase synthesis cleavable under neutral conditions

A novel linker cleavable under neutral conditions has been developed for the solid-phase synthesis of base-labile compounds. The linker is comprised of a 3-azidomethyl-4-hydroxybenzyl alcohol moiety, and the azidomethyl group in the linker is readily converted to an aminomethyl group by treatment with a phosphine reagent in the presence of water to result in an intramolecular cyclization to release the compounds. Using the linker, a base-labile dinucleoside methyl phosphate was synthesized on a highly cross-linked polystyrene (HCP) support and cleaved successfully from the resin without decomposition of the product.     

Development of a fluoride-responsive amide bond cleavage device that is potentially applicable to a traceable linker

A fluoride-responsive (FR) amino acid that induces amide bond cleavage upon the addition of a fluoride was developed, and it was applied to an FR traceable linker. By the use of an alkyne-containing peptide as a model of an alkynylated target protein of a bioactive compound, introduction of the FR traceable linker onto the peptide was achieved. Subsequent fluoride-induced cleavage of the linker followed by labeling of the released peptide derivative was also conducted to examine the potential applicability of the FR traceable linker to the enrichment and labeling of alkynylated target molecules.     

Wang resin-type linker containing a nitro group for polymer support oligosaccharide synthesis: polymer-supported glycosyl donor

A nitro-introduced Wang resin-type linker for soluble and insoluble polymer support oligosaccharide synthesis is described. The linker was used for connecting glycosyl donors and polymer supports, and was completely stable under the glycosylation conditions tested. The cleavage of the linker was performed under reductive conditions without affecting the protecting groups to release disaccharides.     

Solid-phase approach to tetrahydroquinolones using a sulfur linker cleaved by SmI2

[reaction: see text] A sulfur alpha-heteroatom-substituted carbonyl (HASC) linker has been utilized in a solid-phase approach to tetrahydroquinolones. The route illustrates the compatibility of the linker system with palladium-catalyzed transformations and its utility for library synthesis. The linker is cleaved by electron transfer from samarium(II) iodide.     

RESONANCE-ENHANCED CARS SPECTROSCOPY OF BILIPROTEINS. INFLUENCE OF AGGREGATION and LINKER PROTEINS ON CHROMOPHORE STRUCTURE IN ALLOPHYCOCYANIN (Mastigocladus laminosus)

Abstract— Resonance-enhanced coherent anti-Stokes Raman spectra (CARS) are reported for monomers and for trimers with and without linker proteins of allophycocyanin isolated from Mastigocladus laminosus. The CARS spectrum of the monomer is independent of the presence of linker proteins and is very similar to that of phycocyanin monomers indicating that the equivalent chromophores exhibit like structures in both biliproteins. Large differences are, however, observed between the spectra of phycocyanin trimers and those of allophycocyanin trimers with or without linker proteins (L_c^8,9). The observed differences between monomer and trimer spectra are consistent with a change of the α-chromophore-protein arrangement upon aggregation without linker. If linker proteins are present in the trimer, then additional geometry changes of the β-chromophores are induced; these could relate to a transition from the 15Z- anti to 15Z- syn conformation.     

Vapor‐Phase Linker Exchange of the Metal–Organic Framework ZIF‐8: A Solvent‐Free Approach to Post‐synthetic Modification

Zeolitic imidazolate frameworks (ZIFs) are a sub‐class of metal–organic frameworks (MOFs). Although generally stable, ZIFs can undergo post‐synthetic linker exchange (PSLE) in solution under mild conditions. Herein, we present a novel, solvent‐free approach to post‐synthetic linker exchange through exposure to linker vapor.     

Building addressable libraries: amino acid derived fluorescent linkers

A new amino acid derived fluorescent linker for attaching molecules to the surface of a microelectrode array has been developed. Molecules to be monitored on an array are attached to the C-terminus of the linker, the N-terminus is then used to attach the linker to the array, and the side chain is used to synthesize a fluorescent tag. The fluorescent group is made with a one-step oxidative cycloaddition reaction starting from a hydroxyindole group. The linker is compatible with site-selective Cu(I)-chemistry on the array, it allows for quality control assessment of the array itself, and it is compatible with the electrochemical impedance experiments used to monitor binding events on the surface of the array.     

Versatile Tailoring of Paddle‐Wheel ZnII Metal–Organic Frameworks through Single‐Crystal‐to‐Single‐Crystal Transformations

A new tetracarboxylate ligand having short and long arms formed 2D layer Zn^II coordination polymer 1 with paddle‐wheel secondary building units under solvothermal conditions. The framework undergoes solvent‐specific single crystal‐to‐single crystal (SC‐SC) transmetalation to produce 1_Cu . With a sterically encumbered dipyridyl linker, the same ligand forms non‐interpenetrated, 3D, pillared‐layer Zn^II metal–organic framework (MOF) 2 , which takes part in SC‐SC linker‐exchange reactions to produce three daughter frameworks. The parent MOF 2 shows preferential incorporation of the longest linker in competitive linker‐exchange experiments. All the 3D MOFs undergo complete SC‐SC transmetalation with Cu^II, whereby metal exchange in different solvents and monitoring of X‐ray structures revealed that bulky solvated metal ions lead to ordering of the shortest linker in the framework, which confirms that the solvated metal ions enter through the pores along the linker axis.     

The development and preparation of the 2,4-dimethoxybenzyl arylhydrazine (DMBAH) "latent" safety-catch linker: solid phase synthesis of ketopiperazines

The development and preparation of the 2,4-dimethoxybenzyl arylhydrazine (DMBAH) linker 3, a new class of "latent" safety-catch linker which is stable under Mitsunobu alkylation conditions and in the presence of amines and hydrazine, is reported. The utility of the new linker is exemplified by the synthesis of ketopiperazines (MKPs) 24 bearing up to four points of diversity using a cyclitive cleavage approach.     

Effects of bifunctional linker on the optical properties of ZnO nanocolumn-linker-CdSe quantum dots heterostructure

We study the effects of bifunctional linker on the optical properties of ZnO nanocolumn-linker-CdSe quantum dots heterostructure. The CdSe quantum dots are anchored on the surface of ZnO nanocolumns through either aliphatic linker of 3-aminopropyl trimethoxysilane (APS) or aromatic linker of p-aminophenyl trimethoxysilane (APhS). X-ray photoelectron spectroscopy is used to confirm the bifunctional linker bound onto CdSe quantum dots and onto the ZnO nanocolumns. The TEM study reveals a CdSe quantum dot shell of about 15 nm coated on the ZnO nanocolumns. The photoluminance (PL) spectroscopy and time-resolved PL spectroscopy of ZnO nanocolumn-linker-CdSe quantum dots reflects that the photo-induced electron transfer across the interface of ZnO and CdSe through the aromatic APhS is more efficient than the aliphatic APS. This study demonstrates that through the usage of appropriate surface linker, the charge transfer rate across the interfaces of donor/acceptor (D/A) heterostructure can be improved for potential photovoltaic cell applications.     

Chemiluminescent probe for the in vitro detection of protease activity

A strategy involving the use of a self-immolative linker has been investigated for the chemiluminescent sensing of proteases. The reactive linker enabled the release of a 1,2-dioxetane light precursor. As a proof of principle, caspase-3, a key peptidase involved in apoptosis has been targeted. An in vitro assay has been carried out and proved the decomposition of the linker and the selectivity for caspase-3.