Synthetic peptides offer enormous potential to encode the assembly of molecular electronic components, provided that the complex range of interactions is distilled into simple design rules. Here, we report a spectroscopic investigation of aggregation in an extensive series of peptide-perylene diiimide conjugates designed to interrogate the effect of structural variations. By fitting different contributions to temperature dependent optical absorption spectra, we quantify both the thermodynamics and the nature of aggregation for peptides by incrementally varying hydrophobicity, charge density, length, as well as asymmetric substitution with a hexyl chain, and stereocenter inversion. We find that coarse effects like hydrophobicity and hexyl substitution have the greatest impact on aggregation thermodynamics, which are separated into enthalpic and entropic contributions. Moreover, significant peptide packing effects are resolved via stereocenter inversion studies, particularly when examining the nature of aggregates formed and the coupling between π electronic orbitals. Our results develop a quantitative framework for establishing structure-function relationships that will underpin the design of self-assembling peptide electronic materials.

Polymersomes provide a good platform for targeted drug delivery and the creation of complex (bio)catalytically active systems for research in synthetic biology. To realize these applications requires both spatial control over the encapsulation components in these polymersomes and a means to report where the components are in the polymersomes. To address these twin challenges, we synthesized the protein-polymer bioconjugate PNIPAM-b-amilFP497 composed of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and a green-fluorescent protein variant (amilFP497). Above 37 °C, this bioconjugate forms polymersomes that can (co-)encapsulate the fluorescent drug doxorubicin and the fluorescent light-harvesting protein phycoerythrin 545 (PE545). Using fluorescence lifetime imaging microscopy and Förster resonance energy transfer (FLIM-FRET), we can distinguish the co-encapsulated PE545 protein inside the polymersome membrane while doxorubicin is found both in the polymersome core and membrane.

Polymersomes provide agood platform for targeted drug delivery and the creation of complex (bio)catalytically active systems for researchinsynthetic biology.Torealize these applications requires both spatial control over the encapsulation components in these polymersomes and ameans to report where the components are in the polymersomes.T oa ddress these twin challenges,w es ynthesized the protein-polymer bioconjugate PNIPAM-b-amilFP497 composed of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and ag reen-fluorescent protein variant (amilFP497). Above 37 8 8C, this bioconjugate forms polymersomes that can (co-)encapsulate the fluorescent drug doxorubicina nd the fluorescent light-harvesting protein phycoerythrin 545 (PE545). Using fluorescence lifetime imaging microscopya nd Fçrster resonance energy transfer (FLIM-FRET), we can distinguish the co-encapsulated PE545 protein inside the polymersome membrane while doxorubicin is found both in the polymersome core and membrane.

Medulloblastoma is a malignant brain tumor diagnosed in children. Chemotherapy has improved survival rates to approximately 70%; however, children are often left with long-term treatment side effects. New therapies that maintain a high cure rate while reducing off-target toxicity are required. We describe for the first time the use of a bacteriophage-peptide display library to identify heptapeptides that bind to medulloblastoma cells. Two heptapeptides that demonstrated high [E1-3 (1)] or low [E1-7 (2)] medulloblastoma cell binding affinity were synthesized. The potential of the peptides to deliver a therapeutic drug to medulloblastoma cells with specificity was investigated by conjugating E1-3 (1) or E1-7 (2) to doxorubicin (5). Both peptide−drug conjugates were cytotoxic to medulloblastoma cells. E1-3 doxorubicin (3) could permeabilize an in vitro blood− brain barrier and showed a marked reduction in cytotoxicity compared to free doxorubicin (5) in nontumor cells. This study provides proof-of-concept for developing peptide−drug conjugates to inhibit medulloblastoma cell growth while minimizing offtarget toxicity.

The fold of ap rotein is encoded by its amino acid sequence,b ut how complex multimeric proteins fold and assemble into functional quaternary structures remains unclear.H ere we show that two structurally different phycobiliproteins refold and reassemble in ac ooperative manner from their unfolded polypeptide subunits,w ithout biological chaperones.R efolding was confirmed by ultrafast broadband transient absorption and two-dimensional electronic spectroscopyt op robe internal chromophores as am arker of quaternary structure.O ur results demonstrate ac ooperative,s elfchaperone refolding mechanism, whereby the b-subunits independently refold, therebyt emplating the folding of the asubunits,w hich then chaperone the assembly of the native complex, quantitatively returning all coherences.O ur results indicate that subunit self-chaperoning is ar obust mechanism for heteromeric protein folding and assembly that could also be applied in self-assembled synthetic hierarchical systems.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: http://dx.

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The survival of all photosynthetic organisms relies on the initial light harvesting step, and thus, after ~3 billion years of evolution energy capture and transfer has become a highly efficient and effective process. Here we examine the latest developments on understanding light harvesting, particularly in systems that exhibit an ultrafast energy transfer mechanism known as quantum coherence. With increasing knowledge of the structural and function parameters that produce quantum coherence in photosynthetic organisms, we can begin to replicate this process through biomimetic systems providing a faster and more efficient approach to harvesting and storing solar power for the worlds energy needs. Importantly, synthetic systems that display signs of quantum coherence have also been created and the first design principles for synthetic systems utilising quantum coherence are beginning to emerge. Recent claims that quantum coherence also plays a key role in ultrafast charge-separation highlights the importance for chemists, biologists, and material scientists to work more closely together to uncover the role of quantum coherence in photosynthesis and solar energy research.

The fold of ap rotein is encoded by its amino acid sequence,b ut how complex multimeric proteins fold and assemble into functional quaternary structures remains unclear.H ere we show that two structurally different phycobiliproteins refold and reassemble in ac ooperative manner from their unfolded polypeptide subunits,w ithout biological chaperones.R efolding was confirmed by ultrafast broadband transient absorption and two-dimensional electronic spectroscopyt op robe internal chromophores as am arker of quaternary structure.O ur results demonstrate ac ooperative,s elfchaperone refolding mechanism, whereby the b-subunits independently refold, therebyt emplating the folding of the asubunits,w hich then chaperone the assembly of the native complex, quantitatively returning all coherences.O ur results indicate that subunit self-chaperoning is ar obust mechanism for heteromeric protein folding and assembly that could also be applied in self-assembled synthetic hierarchical systems.The folding of proteins was shown to be encoded by amino acids in 1960s.[1] Cooperativity [2][3][4] and the realization that multiple folding pathways are possible [5] are the keys to resolving Levinthalsf amous paradox, [6] which states that if aprotein were to explore all possible conformations,itwould take longer than the age of the universe to fold-yet most proteins fold within seconds.M any proteins in nature are found as multimeric or quaternary complexes, [7] with database searches suggesting that more than 80 %o fp roteins are multimeric,w ith between 15-50 %b eing hetero-oligomeric. [8,9] Thep revailing view on how these complexes form starts with the assumption that the individual subunits are first folded, or sometimes disordered (fuzzy), prior to the oligomerization step. [8,10] Thef olded monomer of the homooligmeric GroEL chaperonin catalyzes its own oligomerization [11] in aprocess known as self-chaperoning.Such behavior has also been observed in the folding of the bI5 RNAi ntron with its CBP2 protein cofactor.[12] How,o ri f, quaternary structures can be unfolded and then refolded in vitro,a nd whether the subunits need each other to fold and form aquaternary structure,r emains an open question.There are two different quaternary types of phycobiliproteins in the cryptophytes,the closed-form and the open-form protein. Both quaternary structures share the same types of subunits,t hat of two identical approximately 20 kDa bsubunits,a nd two identical or non-identical approximately 7-9 kDa a-subunits,w hich combine to make the approximately 60 kDa abab-heterodimer ( Figure S1). The Rhodomonas sp.p hycobiliprotein, phycoerythrin 545 (PE545 [13] ), is ad imer of two non-identical ab-monomers (a 1 ba 2 b,F igure 1a,P DB:1 XF6 [14] ). Each globular b-subunit covalently binds three linear tetrapyrroles (bilins), while the two nonidentical a-subunits (a 1 and a 2 )a re short extended polypeptides,each with asingle covalently bound bilin chromophore. Thed imer adopts the closed-form quaternary structure that brings two chrom...