Peptoids with aliphatic sidechains as helical structures without hydrogen bonds and collagen/ inverse-collagen type structures

Aliphatic homo-polypeptoids of NAla, NVal, NIle and NLeu both in the presence and absence of protecting groups adopt helical structures without hydrogen bonds with Φ, Ψ values of ~ 0, ± 90° with trans amide bonds. These structures are stabilized by carbonyl-carbonyl interactions and characterized by ~ 3.16 residues per turn with a pitch of ~ 6.13 ?. It has been shown that like polyvaline and polyleucine peptides, poly-peptoids can also be exploited for the construction of potential surfactant like molecules by incorporating charged amino acid residues at the N terminal. A single-handed template with Φ, Ψ values of ~ 0, 90° can be attained by incorporating L-leu or L-val at the C-terminal of poly-NIle. Analysis of the simulation results in water as a function of time reveals that the opening of helical structures without hydrogen bonds takes place at sub-picosecond time scale starting from the N-terminal. This leads to the formation of collagen or inverse-collagen type structures (Φ, Ψ ~ -60, 145° and 60, -145° respectively) stabilized by interactions of water molecules with the backbone carbonyl groups.

Assembly of highly efficient aqueous light-harvesting system from sequence-defined peptoids for cytosolic microRNA detection

Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.

Synthesis and biological evaluation of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer

Tetrahydroisoquinoline derivatives were synthesized and their multidrug resistance reversal activities were evaluated in vitro. The results showed that some of the synthetic compounds had higher multidrug resistance （MDR） reversal activities than verapamil.

Synthesis of Peptoid Nucleic Acid with Thymine as Nucleic Base

The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.

Azobenzene-based ultrathin peptoid nanoribbons for the potential on highly efficient artificial light-harvesting

The development of artificial light-harvesting systems based on long-range ordered ultrathin organic nanomaterials(i.e., below3 nm), which were assembled from stimuli-responsive sequence-controlled biomimetic polymers, remains challenging. Herein,we report the self-assembly of azobenzene-containing amphiphilic ternary alternating peptoids to construct photo-responsive ultrathin peptoids nanoribbons(UTPNRs) with a thickness of ~2.3 nm and the length in several micrometers. The pendants hydrophobic conjugate stacking mechanism explained the formation of one-dimensional ultrathin nanostructures, whose thickness was highly dependent on the length of side groups. The photo-isomerization of azobenzene moiety endowed the aggregates with a reversible morphology transformation from UTPNRs to spherical micelles(46.5 nm), upon the alternative irradiation with ultraviolet and visible light. Donor of 4-(2-hydroxyethylamino)-7-nitro-2,1,3-benzoxadiazole(NBD) and acceptor of rhodamine B(RB) were introduced onto the hydrophobic and hydrophilic regions, respectively, to generate photocontrollable artificial light-harvesting systems. Compared with the spheres-based systems, the obtained NBD-UTPNRs@RB composite proved a higher energy transfer efficiency(90.6%) and a lower requirement of RB acceptors in water. A proof-ofconcept use as fluorescent writable ink demonstrated the potential of UTPNRs on information encryption.

Telechelic Triblock Poly(α-Amino Acid)-Poly(Tetrahydrofuran)-Poly(α-Amino Acid)Copolymers:Chain-End Transformation,Polymerization and pH-Responsive Hydrolysis

Main observation and conclusion Block copolymers not only combine properties of different segments but also generate new application prospects.Poly(α-amino acid)-b-poly(tetrahydrofuran)-b-poly(α-amino acid)(PAA-PTHF-PAA)is one of the copolymers.In this contribution,di-hydroxyl-ended HO-PTHF-OH is transferred into di-oxyamino-ended H2NO-PTHF-ONH2 quantitatively,which is used as a macroinitiator to polymerize sarcosine N-thiocarboxyanhydride(Sar-NTA)and N-phenyoxycarbonyl N-ε-carbobenzyloxy-D-lysine(ZDL-NPC).Well-defined triblock PAA-NHO-PTHF-ONH-PAA is produced with high molecular weight(up to 25.3 kg/mol)and narrow dispersity.The amphiphilic PSar-NHO-PTHF-ONH-PSar(STS)self-assembles into micelles with uniform diameters of 30—40 nm according to DLS.Owing to oxygen amide groups inside the backbone of these copolymers,the polyether-poly(amino acid)s block copolymers are cleavable under an acidic environment and therefore have potential applications in smart biomedicine and engineering.

Biomimetic ultrathin pepsomes for photo-controllable catalysis

Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry.However,the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge.Herein,we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle(pepsomes)with an average diameter of∼180 nm.Both cryo-transmission electron microscopy(TEM)and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around∼1.6 nm.The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet(UV)and visible lights,which was attributable to the photoisomerization virtue of azobenzene moiety.As a proof-of-concept,the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol.Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles.Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis.

Peptoid-based hierarchically-structured biomimetic nanomaterials: Synthesis, characterization and applications

Peptoids(or poly-N-substituted glycines)are a promising class of bioinspired sequence-defined polymers due to their highly efficient synthesis,high chemical stability,enzyme hydrolysis resistance,and biocompatibility.By tuning the side chain chemistry of peptoids,it allows for precise control over sequences and achieving a large side-chain diversity.Due to these unique features,in the last several years,many amphiphilic peptoids were designed as highly tunable building blocks for the preparation of biomimetic nanomaterials with well-defined hierarchical structures and desired functionalities.Herein,we provide an overview of the recent achievements in this area by dividing them into the following three aspects.First,mica-and silica-templated peptoid selfassembly are summarized.The presence of inorganic substrates provides the guarantee of investigating their selfassembly mechanisms and interactions between peptoids and substrates using nanoscale characterization techniques,particularly in situ atomic force microscopy(AFM)and AFMbased dynamic force spectroscopy(AFM-DFS).Second,solution-phase self-assembly of peptoids into nanotubes and nanosheets is presented,as well as their self-repair properties.Third,the applications of peptoid-based nanomaterials are outlined,including the construction of catalytic nanomaterials as a template and cytosolic delivery as cargoes.

Investigation of Peptoid Chiral Stationary Phases Terminated with N＇-Substituted PhenyI-L-proline/leucine Amide

Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio- meric separations on CSPs terminated with p-methylphenyl, p-chlorophenyl and unsubstituted phenyl. For short peptoid selectors containing only one S-N-（1-phenylethyl） glycine （Nspe） unit, the terminal p-methyl substituent did not affect chiral recognition abilities significantly. In L-proline amide terminated CSPs, p-chloro substituent resulted in obviously inferior selectivity while in L-leucine amide terminated CSPs, it worked much better. Longer peptoid selectors containing two more Nspe units generally performed much better than the shorter ones, due to the great contributions of peptoid chain to chiral recognition. Meanwhile, the effects of the terminal substituent on selectivity were found changed on these CSPs. For CSPs terminated with L-leucine amide, the terminal p-chloro substituent in longer selector no longer produced the best recognition ability; the CSP with unsubstituted phenyl instead performed best. Comparison of these peptoid CSPs varied in terminal substituents and chain length was conducted to gain a better understanding of the chiral recognition mechanism of this type CSP and promote the development of more useful CSPs.

Blockade of CD28 by a synthetical peptoid inhibits T-ce proliferation and attenuates graft-versus-host disease

CD28 is one of the costimulatory molecules crucial for T-cell activation and thus has become an attractive target for therapeutic immunomodulation. Conventional strategies for blocking CD28 activity using monoclonal antibodies, Fab fragments, antagonistic peptide and fusion proteins, have apparent disadvantages such as inherent immunogenicity, unwanted Fc signaling, poor tissue penetration and bioinstability. Recent research has been directed toward the creation of non-natural, sequence-specific biomimetic oligomers with bioinspired structures that capture the amino-acid interface of the targeted proteins. One such family of molecules is the poly-N-substituted glycines or peptoids, which have close structural similarity to peptides but are essentially invulnerable to protease degradation. To screen for peptoids that specifically target CD28, we first designed and chemically synthesized 19 candidate peptoids based on molecular modeling and docking. Using the phage-displaying system that expresses the extracellular domain of the CD28 homodimer and contains the core B7-binding motif, a peptoid （No. 9） with a molecular formula of C21H29N307, was identified to display the highest binding activity to CD28. This peptoid not only inhibited the lymphocyte proliferation in vitro, but suppressed immunoresponses against alloantigens in vivo, and attenuated the graft-versus-host disease in a mouse bone-marrow transplantation model. These results suggested that peptoids targeting CD28 are effective agents for blocking the CD28-mediated costimulation and suitable for development of novel therapeutic approaches for diseases involving this pathway.